前列腺癌预后的方法与流程

本发明涉及以下方法，其用于确定用于诊断患有前列腺癌的患者的基因表达签名例如以建立针对这样的患者的预后、用于例如在初级处置之后确定所述患者发展侵袭性或惰性疾病的倾向、和/或用于针对可用疗法对患者进行识别和分级。本发明也涉及在这样的方法中使用的产品，例如，套件(kit)、软件等。本发明还涉及用于在对已经在本文中所公开的方法的任意方法中被诊断、识别或分级的患者的处置中使用的疗法。
背景技术：
：：癌症是细胞群组表现出不受控制的生长、侵袭并且有时转移的一类疾病。癌症的这三种恶性属性将其与自限性的、不会侵入或转移的良性肿瘤区分开来。前列腺癌(pca)是男性中最常发生的非皮肤性恶性肿瘤，在2008年全球确诊估计900000例新发病例。由于人口老龄化，pca的发病率在未来数年将会急剧增加。通过确定前列腺特异性抗原(psa)的血液水平、直肠指检(dre)和经直肠超声分析(trus)进行的常规诊断导致对非癌性、良性前列腺状况的显著的首要过度诊断：单在美国每年执行1百万例前列腺活检发现大约250000例新病例，其中大约75％是不必要进行的，这导致患者出现严重并发症(尿脓毒血症、出血、尿潴留)并且总费用>20亿美元(每个活检流程～2100美元)。活检为阴性的100位男性中至少有4位可能由于副作用而住院治疗，并且10000位活检患者中有9位存在由于当前使用的流程而死亡的风险。在美国每年约250000例新检测出的pca病例中，大约200000例最初被表征为局限性疾病，即，限于前列腺器官的癌症。这种状况在一定程度上能通过诸如放射治疗的初级处置方法来治愈或者具体地通过手术(前列腺移除术)对前列腺的部分或全部移除。然而，这些介入通常具有严重的副作用，特别是尿失禁和/或勃起功能障碍，这是前列腺移除术的非常常见的后果。高达50％的经受根治性前列腺移除术的男性会发展成尿失禁。研究已经表明，手术之后一年，15％至50％之间的男性仍然报告有这样的问题。勃起问题同样是根治性前列腺移除术(rp)的严重副作用。仅大约一半的经手术的男性能够恢复其一些勃起能力。此外，针对局部pca的所有常规施加的处置都是昂贵的(通常在20-30000美元左右)，并且每年在美国发生50亿美元的总直接成本。在美国，诊断具有临床局限性疾病的～200000位男性中，高达50％具有非常低或低的癌症风险。因此，nccn(国家综合癌症网络)最近修订了其pca处置指南，以扩展主动监管(as)作为针对患有这样的低风险疾病的患者的温和并且方便的处置备选方案。通过将适当的患者转诊至as，针对这样的患者的生活质量与经受初级处置的男性相比得到显著改善，并且据报导，针对as的5年费用低于每位患者10000美元。此外，在选择手术(相对于as)作为针对给定患者的处置选择的情况下，根据患者的肿瘤的潜在侵袭性对手术程度进行分级是显著有利的。例如，保留神经的手术技术可以更一般性地应用于具有预测低风险疾病的男性，以使根治性前列腺移除术的效力相关的副作用最小化。类似地，根据欧洲泌尿学会(eau)最新的前列腺癌指南，在预测高风险癌症的情况下推荐扩展的淋巴结清除，尽管该流程与更受限的流程相比是复杂、耗时并且与较高的并发症率相关联的。因此，尽管受限较少的淋巴结清除显示错过大约50％的淋巴结转移，但对局部前列腺癌患者的管理需要对个体肿瘤的侵袭性潜力的高度准确的手术前预测，以提供针对每位患者的最佳护理。us2013/196321a1描述了分子测定，其包括测量来自前列腺癌患者的样本中的一个或多个基因的表达水平，以提供关于临床结果的可能性的信息、识别风险分类、并且促进处置决策制定。该参考文献公开了在这样的测定中待分析的许多基因，其被标准化为例如持家基因。此外，也公开了包括用于执行测定的基因特异性探针和/或引物的套件，以及用于执行对表达水平的分析的基于计算机的系统、算法和计算机程序产品。mimotorei等人在cancerletters(2013)，第339卷，第2期，第214-225页上的文章“dyrk2controlstheepithelial-mesenchymaltransitioninbreastcancerbydegradingsnail”中公开了dyrk2在人类乳腺癌组织中被下调并且具有低dyrk2表达肿瘤的患者比具有高syrk2表达肿瘤的那些患者具有更差的结果。作者的结论是，dyrk2是乳腺癌的潜在预后指标，并且另外提到了，dyrk2也已经被发现在肺癌、结肠癌和前列腺癌中被下调。wo2010/131194a1涉及pde4d7作为恶性激素敏感性前列腺癌的指标，并且公开了用于诊断、检测、监测和预测恶性激素敏感性前列腺癌的方法，其包括确定pde4d7的水平的步骤。另外，描述了用于识别适合特定癌症疗法的个体的方法，以及用于执行该方法的复合物，包括针对pde4d7表达产物特异性的寡核苷酸或探针。wo2014/153442a2公开了用于对卵巢癌的诊断、预后和处置的方法，其涉及确定特定指标基因的表达水平。所述表达水平被转换成指数，其中，利用从上调基因中的一些上调基因中减去下调基因的表达水平对基因进行平均地加权。技术实现要素：本发明涉及识别和使用与前列腺癌临床相关的感兴趣生物标记基因(也被称为标记基因)的基因表达谱、签名或模式。具体地，本发明基于对从生物学样本获得的核酸(优选为生物标记基因的转录物)的基因表达分析，以及对与侵袭性和惰性疾病、患者生存和前列腺癌复发相关的生物标记基因的识别。对这些标记基因的表达分析能够被用于提供前列腺癌进展指数(pcpi)，其能够被用于将患者分类为具有侵袭性和惰性疾病以及具有对应的不良或良好预后。此外，pcpi也能够被用于预测在先前被临床诊断和处置的对象的疾病的进展，并且被用于根据其个体pcpi对患者进行分级。因此，pcpi为与前列腺癌患者的诊断、预后和处置有关的个性化医学提供非常有用的参数。pcpi可以单独使用或者可以与提供关于患者个人疾病状态或疾病阶段的信息的其他手段和方法结合使用。医师和/或病理学家能够有利地使用pcpi来确认在用于对患者(例如，具有发展侵袭性与惰性前列腺癌形式的倾向的患者)进行诊断、识别、预后、分类和/或分级的其他方法中所获得的结果。因此，由本发明所提供的方法和手段帮助建立更好的诊断、预后等，从而找到针对患者的最佳处置，并且避免由于副作用而危险的不必要的手术或其他处置，其有时甚至是多余的并且导致巨大的公共卫生系统成本。本发明的一方面涉及一种方法，包括：确定针对以下签名基因的基因表达水平：azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2、col1a1、col3a1、col5a2、inhba、thbs2、vcan、bgn、birc5和dyrk2、以及任选地包括pde4d5和/或pde4d7的pde4异构体，以获得针对对象的对象表达谱。在一些实施例中，所述方法还包括：基于所述对象表达谱将所述对象分类为前列腺癌阳性或前列腺癌阴性；和/或基于所述对象表达谱将所述对象分类为具有对前列腺癌的良好预后或不良预后，其中，所述良好预后预测在初始诊断之后的预定时段内生存的可能性增加和/或在初级处置之后疾病没有进展，而所述不良预后预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加；和/或基于所述对象表达谱将所述对象分类为具有或者不具有易遭受疾病进展影响的前列腺癌的倾向，其中，所述倾向预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加。在一个实施例中，所述方法还包括：基于所述对象表达谱将所述对象分类为前列腺癌阳性或前列腺癌阴性；或者基于所述对象表达谱将所述对象分类为具有对前列腺癌的良好预后或不良预后，其中，所述良好预后预测在初始诊断之后的预定时段内生存的可能性增加和/或在初级处置之后疾病没有进展，而所述不良预后预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加；或者基于所述对象表达谱将对象分类为具有或不具有易遭受疾病进展影响的前列腺癌的倾向，其中，所述倾向预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加。在一个实施例中，所述方法还包括：基于所述对象表达谱将所述对象分类为前列腺癌阳性或前列腺癌阴性；或者基于所述对象表达谱将所述对象分类为具有对前列腺癌的良好预后或不良预后，其中，所述良好预后预测在初始诊断之后的预定时段内生存的可能性增加和/或在初级处置之后疾病没有进展，而所述不良预后预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加；并且基于所述对象表达谱将所述对象分类为具有或不具有易遭受疾病进展影响的前列腺癌的倾向，其中，所述倾向预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加。在一个实施例中，所述方法还包括：基于所述对象表达谱将所述对象分类为前列腺癌阳性或前列腺癌阴性；并且基于所述对象表达谱将所述对象分类为具有对前列腺癌的良好预后或不良预后，其中，所述良好预后预测在初始诊断之后的预定时段内生存的可能性增加和/或在初级处置之后疾病没有进展，而所述不良预后预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加；或者基于所述对象表达谱将所述对象分类为具有或不具有易遭受疾病进展影响的前列腺癌的倾向，其中，所述倾向预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加。在一个实施例中，所述方法还包括：基于所述对象表达谱将所述对象分类为前列腺癌阳性或前列腺癌阴性；并且基于所述对象表达谱将所述对象分类为具有对前列腺癌的良好预后或不良预后，其中，所述良好预后预测在初始诊断之后的预定时段内生存的可能性增加和/或在初级处置之后疾病没有进展，而所述不良预后预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加；并且基于所述对象表达谱将所述对象分类为具有或不具有易遭受疾病进展影响的前列腺癌的倾向，其中，所述倾向预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加。本发明的另一方面涉及一种方法，包括：基于针对对象的对象表达谱将所述对象分类为前列腺癌阳性或前列腺癌阴性，其中，所述对象表达谱包括以下签名基因的基因表达水平：azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2、col1a1、col3a1、col5a2、inhba、thbs2、vcan、bgn、birc5和dyrk2、以及任选地包括pde4d5和/或pde4d7的pde4异构体；和/或基于针对对象的对象表达谱将所述对象分类为具有良好预后或不良预后，其中，所述对象表达谱包括以下签名基因的基因表达水平：azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2、col1a1、col3a1、col5a2、inhba、thbs2、vcan、bgn、birc5和dyrk2、以及任选地包括pde4d5和/或pde4d7的pde4异构体，并且其中，良好预后预测在初始诊断之后的预定时段内生存的可能性增加和/或在初级处置之后疾病没有进展，而不良预后预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加；和/或基于针对对象的对象表达谱将所述对象分类为具有或不具有易遭受疾病进展影响的前列腺癌的倾向，其中，所述对象表达谱包括以下签名基因的基因表达水平：azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2、col1a1、col3a1、col5a2、inhba、thbs2、vcan、bgn、birc5和dyrk2、以及任选地包括pde4d5和/或pde4d7的pde4异构体，其中，所述倾向预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加。在一个实施例中，一种方法，包括：基于针对对象的对象表达谱将所述对象分类为前列腺癌阳性或前列腺癌阴性，其中，所述对象表达谱包括以下签名基因的基因表达水平：azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2、col1a1、col3a1、col5a2、inhba、thbs2、vcan、bgn、birc5和dyrk2、以及任选地包括pde4d5和/或pde4d7的pde4异构体；或者基于针对对象的对象表达谱将所述对象分类为具有良好预后或不良预后，其中，所述对象表达谱包括以下签名基因的基因表达水平：azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2、col1a1、col3a1、col5a2、inhba、thbs2、vcan、bgn、birc5和dyrk2、以及任选地包括pde4d5和/或pde4d7的pde4异构体，并且其中，良好预后预测在初始诊断之后的预定时段内生存的可能性增加和/或在初级处置之后疾病没有进展，而不良预后预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加；或者基于针对对象的对象表达谱将对象分类为具有或不具有易遭受疾病进展影响的前列腺癌的倾向，其中，所述对象表达谱包括以下签名基因的基因表达水平：azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2、col1a1、col3a1、col5a2、inhba、thbs2、vcan、bgn、birc5和dyrk2，本文任选地包括pde4d5和/或pde4d7的pde4异构体，其中，所述倾向预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加。在一个实施例中，一种方法包括：基于针对对象的对象表达谱将所述对象分类为前列腺癌阳性或前列腺癌阴性，其中，所述对象表达谱包括以下签名基因的基因表达水平：azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2、col1a1、col3a1、col5a2、inhba、thbs2、vcan、bgn、birc5和dyrk2、以及任选地包括pde4d5和/或pde4d7的pde4异构体；或者基于对象的对象表达谱将所述对象分类为具有良好预后或不良预后，其中，所述对象表达谱包括以下签名基因的基因表达水平：azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2、col1a1、col3a1、col5a2、inhba、thbs2、vcan、bgn、birc5和dyrk2、以及任选地包括pde4d5和/或pde4d7的pde4异构体，并且其中，良好预后预测在初始诊断之后的预定时段内生存的可能性增加和/或在初级处置之后疾病没有进展，而不良预后预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加；并且基于针对对象的对象表达谱将所述对象分类为具有或不具有易遭受疾病进展影响的前列腺癌的倾向，其中，所述对象表达谱包括以下签名基因的基因表达水平：azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2、col1a1、col3a1、col5a2、inhba、thbs2、vcan、bgn、birc5和dyrk2、以及任选地包括pde4d5和/或pde4d7的pde4异构体，其中，所述倾向预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加。在一个实施例中，一种方法，包括：基于针对对象的对象表达谱将所述对象分类为前列腺癌阳性或前列腺癌阴性，其中，对象表达谱包括以下签名基因的基因表达水平：azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2、col1a1、col3a1、col5a2、inhba、thbs2、vcan、bgn、birc5和dyrk2、以及任选地包括pde4d5和/或pde4d7的pde4异构体；并且基于针对对象的对象表达谱将所述对象分类为具有良好预后或不良预后，其中，所述对象表达谱包括以下签名基因的基因表达水平：azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2、col1a1、col3a1、col5a2、inhba、thbs2、vcan、bgn、birc5和dyrk2、以及任选地包括pde4d5和/或pde4d7的pde4异构体，并且其中，良好预后预测在初始诊断之后的预定时段内生存的可能性增加和/或在初级处置之后疾病没有进展，而不良预后预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加；或者基于针对对象的对象表达谱将所述对象分类为具有或不具有易遭受疾病进展影响的前列腺癌的倾向，其中，所述对象表达谱包括以下签名基因的基因表达水平：azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2、col1a1、col3a1、col5a2、inhba、thbs2、vcan、bgn、birc5和dyrk2、以及任选地包括pde4d5和/或pde4d7的pde4异构体，其中，所述倾向预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加。在一个实施例中，一种方法，包括：基于针对对象的对象表达谱将所述对象分类为前列腺癌阳性或前列腺癌阴性，其中，所述对象表达谱包括以下签名基因的基因表达水平：azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2、col1a1、col3a1、col5a2、inhba、thbs2、vcan、bgn、birc5和dyrk2、以及任选地包括pde4d5和/或pde4d7的pde4异构体；并且基于针对对象的对象表达谱将所述对象分类为具有良好预后或不良预后，其中，所述对象表达谱包括以下签名基因的基因表达水平：azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2、col1a1、col3a1、col5a2、inhba、thbs2、vcan、bgn、birc5和dyrk2、以及任选地包括pde4d5和/或pde4d7的pde4异构体，并且其中，良好预后预测在初始诊断之后的预定时段内生存的可能性增加和/或在初级处置之后疾病没有进展，而不良预后预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加；并且基于针对对象的对象表达谱将所述对象分类为具有或不具有易遭受疾病进展影响的前列腺癌的倾向，其中，所述对象表达谱包括以下签名基因的基因表达水平：azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2、col1a1、col3a1、col5a2、inhba、thbs2、vcan、bgn、birc5和dyrk2、以及任选地包括pde4d5和/或pde4d7的pde4异构体，其中，所述倾向预测在初始诊断之后的预定时段内的侵袭性疾病、生存的可能性降低、生化复发的可能性增加、临床复发的可能性增加、和/或存在局部或远处转移的可能性增加。在本发明各方面的一些实施例中，所述对象是被诊断患有前列腺癌的患者。在本发明各方面的一些实施例中，所述对象表达谱是从来自对象的样本获得的。在本发明各方面的特定实施例中，样本是细胞系。在本发明各方面的一些实施例中，患者是从包括(a)新诊断患有前列腺癌的患者、(b)已经经受针对前列腺癌的初级处置的患者的组中选择的。在本发明各方面的一些实施例中，患者先前被诊断患有临床局部前列腺癌。在本发明各方面的实施例中，所述初级处置是从包括前列腺手术、前列腺移除、放射疗法、化学疗法、有限或扩展淋巴结清除的组中选择的。在本发明各方面的实施例中，组(a)中的患者进一步选自已经经受以下方法中的至少一种方法的新诊断患有前列腺癌的患者：确定前列腺特异性抗原(psa)的血液水平、直肠指检(dre)和经直肠超声分析(trus)、以及前列腺活组织检查。在本发明各方面的一些实施例中，所述预定时段为至少6个月、至少1年、至少2年、至少3年、至少4年、至少5年、至少10年或至少15年。在本发明各方面的一些实施例中，通过使用一个或多个探针和/或一个或多个探针集检测mrna表达来确定基因表达水平。在本发明各方面的一些实施例中，通过基于扩增的方法和/或微阵列分析来确定基因表达水平。在本发明各方面的一些实施例中，通过rna测序、pcr、qpcr或多路复用pcr来确定基因表达水平。在本发明各方面的一些实施例中，所述患者表达谱被转换为前列腺癌进展指数(pcpi)。在实施例中，所述前列腺癌进展指数是根据以下等式来计算的：pcpi＝(gev_av_goi_up)-(gev_av_goi_down)，其中，gev_av_goi_up是上调基因的平均基因表达值，并且其中，gev_av_goi_down是下调基因的平均基因表达值，其中，所述值是基于每个对象样本的标准化基因表达数据来确定的。pcpi计算能够呈现对预后的良好预测或者如在本文中所描述的在其他临床应用中的良好性能。在本发明各方面的一些实施例中，将一组签名基因的表达水平标准化为参考基因的表达，优选地，其中，所述参考基因是持家基因，并且更优选地，其中，所述持家基因是tbp、hprt1、actb、rplp0、pum1、polr2a或b2m。在本发明的特定实施例中，当选自包括col1a1、col3a1、col5a2、inhba、thbs2、vcan、bgn、birc5、dyrk2的组中的任意一个或多个基因的表达与控制样本中的对应基因表达水平相比被上调时，并且其中，当选自包括azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2的组中的任意一个或多个基因的表达与控制样本中的对应基因表达水平相比被下调时，将所述对象分类为前列腺癌阳性；或者，当选自包括col1a1、col3a1、col5a2、inhba、thbs2、vcan、bgn、birc5、dyrk2的组中的任意一个或多个基因的表达与控制样本中的对应基因表达水平相比被下调时，并且其中，当选自包括azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2和任选的pde4d5和/或pde4d7的组中的任意一个或多个基因与控制样本中对应基因表达相比被上调时，所述对象被分类为前列腺癌阴性。所选择的基因能够呈现在分类中的良好性能。在本发明各方面的一些实施例中，如果所述前列腺癌进展指数低于选定的阈值，则所述对象被分类为具有良好预后，或者如果所述前列腺癌进展指数高于选定的阈值，则所述对象被分类为具有不良预后；并且/或者，如果所述前列腺癌进展指数高于选定的阈值，则所述对象被分类为具有易遭受疾病进展影响的前列腺癌的倾向，或者如果所述前列腺癌进展指数低于选定的阈值，则所述对象被分类为不具有易遭受疾病进展影响的前列腺癌的倾向。在本发明各方面的一些实施例中，所述方法还包括：根据所确定的预后或所确定的倾向，针对侵袭性疾病与非侵袭性疾病的风险来对对象进行分级；和/或根据所确定的预后或所确定的倾向，向有需要的对象提供合适的癌症处置。在本发明各方面的一些实施例中，所述癌症处置选自：前列腺手术、前列腺移除、放射疗法、化学疗法、近距离放射疗法、有限或扩展的淋巴结移除、或者其组合，优选是激素疗法和放射疗法的组合。在本发明各方面的一些实施例中，不良预后或易遭受疾病进展影响的前列腺癌的倾向指示要利用选自包括以下项的组的处置中的任何一种或多种来处置对象的适用性：前列腺手术、前列腺移除、化学疗法、放射疗法、近距离放射疗法、有限或扩展的淋巴结清除。在本发明各方面的一些实施例中，针对侵袭性前列腺癌的倾向指示对选自包括以下项的组中的处置的适用性：重新活检、前列腺手术、前列腺移除、化学疗法、放射疗法、激素疗法、有限或扩展的淋巴结清除、或其其组合，优选是激素疗法与放射疗法的组合。在本发明各方面的一些实施例中，所述方法还包括向用户接口设备、计算机可读存储介质、监视器或作为网络一部分的计算机显示或输出步骤之一的结果。另一方面涉及一种产品，包括：用于确定针对以下签名基因的基因表达水平的引物和/或探针：azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2、col1a1、col3a1、col5a2、inhba、thbs2、vcan、bgn、birc5和dyrk2、以及任选地包括pde4d5和/或pde4d7的pde4异构体；任选地还包括用于确定除了上文所提到的基因之外的、在图1或图2中所列出的一组基因的表达水平的引物和/或探针；和/或任选地还包括用于确定参考基因的基因表达水平的引物和/或探针，优选地，其中，所述参考基因是持家基因，并且更优选地，其中，所述持家基因是tbp、hprt1、actb、rplp0、pum1、polr2a或b2m。在一些实施例中，所述产品是套件，例如包括pcr套件、rna测序套件或微阵列套件，优选是dna微阵列套件。在另一实施例中，所述产品是微阵列。所述产品能够提供用于确定如在本文中所描述的水平的有效方式，并且因此，能够呈现如在本文中所描述在临床应用中的良好性能。在一些实施例中，所述产品是用于执行本发明方法的产品，或者所述产品是以下产品：用于诊断前列腺癌，用于建立诊断患有前列腺癌的患者的预后，用于将诊断患有前列腺癌的患者进行分级，用于确定在具有前列腺癌的患者中侵袭性或惰性前列腺癌的倾向。在一些实施例中，所述产品是包括一组核酸分子的复合物，每个核酸分子包括至少一个多核苷酸探针序列，用于分析由图1或图2中的任意一个所包括的基因或者如在上文所描述的基因的基因表达。在一些实施例中，所述产物是核酸阵列，其包括，针对一组基因中的每个基因，包括图1或2中所列出的基因的一组基因，或者上文所描述的基因，一个或多个多核苷酸探针互补物和能杂交到基因中的编码序列，用于确定如在上文所定义的前列腺表达谱和/或pcpi。在一些实施例中，所述产品是套件，根据在本文中所描述的方法中的任一种方法，其用于诊断前列腺癌，用于建立针对诊断患有前列腺癌的患者的预后，用于对诊断患有前列腺癌的患者进行分级，用于确定具有前列腺癌的患者中的侵袭性列腺癌或惰性前列腺癌的倾向性，所述产品包括：a)如在本文中所定义的阵列，b)套件控制；以及c)任选的使用指令。在一些实施例中，所述产品是用于对从生物学样品获得的核酸进行表达分析的核酸阵列，其中，所述阵列包括基底，所述基底包括探针，所述探针适合于通过在图1或图2中所提及的基因或者如在上文所描述的基因而特异性结合核酸或者其片段。在一些实施例中，所述产品是用于pcr的制品，包括用于特定地扩增和检测由图1或图2所述的基因或者如在上文所描述的基因编码的核酸或者其片段的成分。本发明的另一方面涉及选自前列腺手术、前列腺移除、放射疗法、激素疗法、化学疗法、有限或扩展的淋巴结清除或者其组合的疗法，用于处置被识别为适合的患者，其中，所述患者被诊断患有本发明的方法所定义的针对侵袭性前列腺癌的倾向。本发明的另一方面涉及一种计算机程序产品，其包括被存储在计算机可读介质上或者能从通信网络下载的计算机可读代码，所述计算机可读代码当在计算机上运行时实施如在本文中所描述的方法中的任意一种方法的一个或多个步骤或者所有步骤。本发明的另一方面涉及在其上存储有可执行程序的非瞬态计算机可读存储介质，其中，所述程序指示微处理器执行本发明的方法中的任何方法的一个或多个步骤。本发明的又一方面涉及一种设备，其用于由图1或图2中所提及的基因或者上文所描述的基因编码的核酸(或其片段)的基因表达分析，其中，所述设备优选包括：a)数据库，其包括包含与临床结果相关联的参考基因表达值的记录，每个参考谱包括在图1或图2中所列出的一组基因或上述基因的表达水平，和/或b)用户接口，其能够接收和/或输入对一组基因的基因表达值的选择，所述组包括在图1或图2中所列出的基因或者如在上文中所描述的基因，用于与数据库中的基因参考表达谱进行比较；c)输出部，其根据该组基因的表达水平来显示临床预后预测。本发明的又一方面涉及用于执行本发明的方法的设备。本发明的另一方面涉及一种系统，其包括本发明的产品以及本发明的计算机程序产品或非瞬态计算机可读存储介质或者本发明的用于核酸的基因表达分析的设备或者执行本发明的方法的设备。附图说明图1示出了包括从公开可用的研究数据导出的经分析的基因候选的表格。图2示出了包括被分析以构建pcpi的57个基因候选的表格。图3示出了关于pcpi_18或pcpi_17预测在针对数据集gse21032、gse41408、gse25136、gse16560、gse10645的初级处置(前列腺手术)之后的10-15年内的远处转移的发展的初级终点的性能的概述。图4示出了pcpi_18预测在针对数据集gse46691的初级处置之后的10-15年内的远处转移发展的初级终点的性能。图5示出了，与标准临床参数(如处置前psa、活检或病理学gleason分数、或者临床/病理疾病阶段)相比较，pcpi_18或pcpi_17在多变量cox回归分析中预测针对数据集gse21032、gse41408、gse16560、gse10645的初级处置(一般是前列腺手术)之后的10-15年内的远处转移发展的初级终点的性能。针对每个个体数据集示出了针对pcpi和个体临床参数的卡方以及风险比。图6示出了pcpi_18预测在针对数据集gse21032、gse41408、gse25136的初级处置(一般为前列腺手术)之后的10-15年内的生化疾病复发(bcr)发展的初级终点的性能的概述。图7示出了，与标准临床参数(如处置前psa、活检或病理学gleason分数、或临床/病理疾病阶段)相比较，pcpi_18在多变量cox回归中预测针对数据集gse21032、gse41408、gse25136的初级处置(一般为前列腺手术)之后的10-15年内的生化疾病复发(bcr)发展的初级终点的性能。图8示出了针对pcpi_18支持对例如针对主动监视(as)或主动处置(例如，前列腺移除术、放射疗法和激素治疗)的患者分级做出临床决策的roc曲线截断分析。图9列出了在本申请中所提到的感兴趣基因，其具有转录物id、蛋白质id以及针对感兴趣基因特异性的引物和探针序列。图10列出了在本申请中所提到的参考基因，其具有转录物id、蛋白质id以及针对参考基因特异性的引物和探针序列。图11示出了针对根据pcpi_19以及能够从美国国家综合癌症网络(nccn)网页指南(https://www.nccn.org/professionals/physician_gls/f_guidelines.asp)推断的nccn临床风险特性而分组的422位患者在5至10年内的不同复发风险的分析。图12示出了根据gpsu分数以及能够从美国国家综合癌症网络(nccn)网页指南(https://www.nccn.org/professionals/physician_gls/f_guidelines.asp)推断出的nccn临床风险特征而分组的407位患者在5至10年内的不同复发风险的分析。图13示出了根据ccp分数以及能够从美国国家综合癌症网络(nccn)网页指南(https://www.nccn.org/professionals/physician_gls/f_guidelines.asp)推断出的nccn临床风险特性而分组的407位患者在5至10年内的不同复发风险的分析。具体实施方式尽管将针对具体实施例来描述本发明，但是该描述不应当被解释为限制性的意义。在详细描述本发明的示范性实施例之前，给出了对于理解本发明重要的定义。如在本说明书和随附的权利要求中所使用的，除非上下文另外明确指出，否则单数形式的“一”和“一个”也包括相应的复数形式。在本发明的上下文中，术语“大约”和“近似”表示本领域技术人员将理解仍然确保所讨论特征的技术效果的准确性的区间。该术语通常指示与所指示的数值的±20％、优选±15％、更优选±10％、并且甚至更优选±5％的偏差。应当理解，术语“包括”不是限制性的。为了本发明的目的，术语“由...组成”被认为是术语“包括”的优选实施例。如果在下文中将组定义为包括至少特定数量的实施例，则这意味着也涵盖优选仅由这些实施例组成的组。此外，在说明书和权利要求中的术语“第一”、“第二”、“第三”或者“(a)”、“(b)”、“(c)”、“(d)”等被用于区分相似的元件，而不一定用于描述顺序或时间次序。应当理解，这样使用的术语在适当情况下是能互换的，并且在本文中所描述的本发明的实施例能够以不同于在本文中所描述或例示的其他顺序来操作。在术语“第一”、“第二”、“第三”或者“(a)”、“(b)”、“(c)”、“(d)”等涉及方法或使用的步骤的情况下，则在这些步骤之间没有时间或时间间隔一致性，即，这些步骤可以同时被执行，或者在这样的步骤之间可以存在数秒、数分钟、数小时、数天、数周、数月或甚至数年的时间间隔，除非如在本申请上文或下文所阐述地在本申请中另外指出。应当理解，本发明不限于在本文中所描述的具体方法、协议、蛋白质、细菌、载体、试剂等，因为这些可以变化。也应当理解，在本文中所使用的术语仅仅是出于描述具体实施例的目的，而并非意图限制本发明的范围，该范围仅由随附的权利要求来限定。除非另外定义，否则在本文在所使用的所有技术和科学术语具有与本领域普通技术人员通常理解的相同的含义。在本发明的上下文中，术语“(一个或多个)签名基因”、(一个或多个)标记基因、或者“感兴趣基因(goi)”能够互换使用，并且指定在本发明的方法中确定其表达水平的生物标记。在本发明的优选实施例中，在本公开的图2中描绘了这些基因，并且在下文以及权利要求中被明确地提及。因此，本发明涉及(一个或多个)标记基因，当将在初级处置之后或者在初始前列腺癌诊断之后获得的前列腺癌组织中的表达与在初始前列腺癌诊断之前和/或在初始前列腺癌特异性处置之前获得的在前列腺癌组织中的表达进行比较时，所述标记基因的表达或者被上调或者被下调。在初级处置之后或者在初始前列腺癌诊断之后获得的组织中的标记基因表达可以与患者结果参数(例如，生化复发、转移的发展、骨癌和/或死亡)相关。当在本发明的方法的上下文中确定表达值时，获得个体化的“基因表达谱”，其反映样本或对象中的goi的基因表达值。在后一种情况下，所述表达值也被称为“对象表达谱”。应当注意，样本表达谱和/或对象表达谱可以随时间而变化。例如，在被诊断有前列腺癌的患者的治疗性处置之前或之后的基因表达谱可能是不同的。类似地，在包含前列腺癌细胞的样本中发现的基因表达谱将不同于在不包含前列腺癌细胞的样本中发现的那些基因表达谱。因此，在本文中所使用的术语“(一个或多个)标记基因”或者“(一个或多个)感兴趣基因”涉及在本文中上文所定义的(一个或多个)基因、(一个或多个)基因单元、或(一个或多个)序列(核苷酸序列)的集合，当与控制水平进行比较时，优选当与在不同时间点处(例如，在初始诊断处，紧接在初级处置之后，或者稍后，即，在初始诊断或初级处置之后的数月或数年)获得的前列腺组织中的表达进行比较时，其表达水平在前列腺癌细胞或组织中或者在包括这样的细胞或组织或者其部分或片段的任何类型的样本中或者被上调或者被下调。该术语指代所述基因单元或序列的任何表达产物，特别指代mrna转录物。当第一次检查标记基因或感兴趣基因时，即，当第一次怀疑患者患有前列腺癌时，也设想到了使用源自正常组织或良性前列腺癌组织的额外控制材料。如在本文中所使用的术语“表达水平”指代能从限定数量的细胞或限定的组织部分导出的(一个或多个)标记基因转录物的量，优选指代在标准核酸(例如，rna)提取流程中能获得的转录物的量。合适的提取方法对于本领域技术人员是已知的。如在本文中所使用的，术语“控制水平”(或“控制状态”)涉及与测试样本同时地和/或在相似或相当的条件下通过使用从已知其状况或疾病状态(例如，非癌症、正常或良性前列腺癌、晚期前列腺癌等)的一位或多位患者先前收集和存储的(一个或多个)样本来确定表达水平。为了确定侵袭性癌症与惰性癌症的倾向性，优选在所获得的癌症组织中确定控制水平以确立初始诊断，然后将其与在稍后阶段(例如，在初级处置之后)确定的goi的表达进行比较。术语“疾病状态”或“癌性疾病状态”涉及在非癌细胞状态与(包括)末期癌细胞状态之间的细胞或分子状态的任何状态或类型。优选地，该术语包括有机体内在(和排除)非癌细胞状态与(包括)末期癌细胞状态之间的不同癌变增殖/发展阶段或肿瘤发展水平。这样的发展阶段可以包括由uicc定义的恶性肿瘤的tnm(肿瘤、结节、转移)分类系统的所有阶段，例如，阶段0和i到iv。该术语也包括在tnm阶段0之前的阶段，例如，在其中本领域技术人员已知的癌症生物标记显示修改的表达或表达模式的发展阶段。如上文所提到的表达水平优选可以是在本文中所定义的(一个或多个)标记基因或goi的表达水平。术语“癌性”在本发明的上下文中涉及如上文所定义的癌性疾病状态。术语“非癌性”在本发明的上下文中涉及其中不能够检测到良性或恶性增殖的状况。用于所述检测的合适的手段在本领域中是已知的。可以通过基于通过在来自已知其疾病状态的对象的样本中分析先前确定的本发明的(一个或多个)标记基因的(一个或多个)表达水平而获得的结果的统计学方法，来确定表达控制水平。此外，能够从来自先前测试的患者、组织或细胞的表达模式或表达水平的数据库中导出所述控制水平。能够根据来源于已经被诊断患有前列腺癌(例如，激素独立或激素抗性前列腺癌)的患者的参考样本来确定控制水平。此外，可以将待测试的生物学样本中的本发明的标记基因的表达水平与多个控制水平进行比较，所述控制水平是根据多个参考样本来确定的。设想到了，使用根据从类似于来源于对象的生物学样本的组织类型导出的参考样本而确定的控制水平。特别优选的是，使用源自如在本文中上文所定义的疾病状态为癌性的患者的(一个或多个)样本。在使用在本文中所描述的标记基因对前列腺癌的一般诊断方法中，也能够确定呈现不能够检测到良性或恶性增殖的健康状况的对象组织中的控制水平。也设想到了，使用来源于患有在本文中上文所定义的良性前列腺癌的一个或多个患者的(一个或多个)样本，即，所述患者呈现能够检测到良性增殖的健康状况。在本文中所使用的术语“良性前列腺癌”指代缺乏癌症的全部三种恶性属性(即，不以无限侵袭性方式生长、不侵入周围组织、并且不转移)的前列腺癌。通常，良性前列腺癌意味着缺乏癌症的侵袭属性的温和并且非进行性前列腺癌或肿胀疾病。此外，良性前列腺癌通常被封装，并且因此抑制其以恶性方式行为的能力。良性肿瘤或健康状况能够通过本领域技术人员已知的任何合适的、独立分子学、组织学或生理学方法来确定。备选地，参考样本可以包括源自细胞系(例如，永生化的癌细胞系)的材料。优选地，源自前列腺癌细胞系的材料根据本发明可以被包括在参考样本中。优选的癌细胞系的范例包括细胞系pc346p、pc346b、lncap、vcap、ducap、pc346c、pc3、du145、pc346cdd、pc346flu1、pc346flu2。在另一优选备选方案中，参考样本可以来源于在临床环境中获得的对象/患者组织或组织系列或组织集合。样本例如可以从正在进行手术的男性患者获得。样本可以来源于任何合适的组织类型，例如，来自前列腺组织或淋巴结。患者组织集合的优选范例来源于外科手术(例如，前列腺移除术)。此外，设想到了使用具有已知疾病状态的群体中(例如，具有良性前列腺癌的群体或健康群体)的本发明的(一个或多个)标记基因的表达水平的标准值。所述标准值能够通过本领域已知的任何方法来获得。例如，可以使用平均值±2sd(标准偏差)或平均值±3sd的范围作为标准值。此外，也能够通过使用先前从已知其疾病状态是癌性的一位或多位患者(即，已经被独立地诊断患有前列腺癌的患者，特别是患有侵袭性前列腺癌的患者)收集并存储的(一个或多个)样本，在与测试样本同时和/或相似或相当的条件下确定控制水平。在本发明的上下文中，从已知不是癌性的生物学样本(例如，健康组织样本或良性前列腺癌样本)所确定的控制水平被称为“正常控制水平”。如果从癌性生物学样本(特别是来自被独立诊断为前列腺癌的患者的样本)确定控制水平，则能将其指定为“癌性控制水平”。术语“前列腺癌”涉及男性生殖系统中的前列腺的癌症，其发生于前列腺细胞突变且开始繁殖失控时。通常，前列腺癌与前列腺特异性抗原(psa)水平升高有关。在本发明的一个实施例中，术语“前列腺癌”涉及示出psa水平高于4.0的癌症。在另一实施例中，该术语涉及示出psa水平高于2.0的癌症。术语“psa水平”指代以ng/ml计的血液中的psa的浓度。术语“前列腺癌”也包括对男性性激素刺激敏感的前列腺癌或前列腺癌细胞系，只要涉及其生长或增殖。术语“敏感性”涉及前列腺癌或前列腺癌细胞系在男性性激素存在下显示生化或细胞反应模式，但确实需要男性性激素用于生长和/或增殖的情况。激素敏感性前列腺因此被理解为恶性前列腺癌，其从如pin(前列腺上皮内瘤)的前恶变形式发展并且其特征在于其生长仍然依赖于男性性激素男性激素的存在。相反，一旦这样的肿瘤被激素损耗治疗所处置，那些癌症通常发展成激素抵抗形式，其生长独立于男性激素的存在。术语“激素抗性前列腺癌”意指前列腺癌或前列腺癌细胞系的生长和增殖对男性性激素刺激具有抗性。该术语也涉及晚期前列腺癌发展阶段，其不再适于施予如在本文中上文所定义的抗激素(优选抗男性激素)给药。在本文中所使用的术语“男性性激素”指代男性激素，优选是睾酮、雄烯二酮、二氢睾酮、脱氢表雄酮、雄烯二醇或雄酮。在另一方面中，本发明涉及使用(一个或多个)标记基因或goi作为诊断、检测、监测或预测恶性、激素敏感的前列腺癌或者朝向前列腺癌的进展的标记。在本发明的上下文中，术语“上调的”或“上调的表达水平”或“表达水平的增加”(可以同义地使用)因此表示在待分析的情况(例如，能源自患者的样本的情况)与参考点之间的表达水平的提高，所述参考点可以是源自本领域技术人员已知的任何合适的前列腺癌或癌症阶段的正常控制水平或癌性控制水平。当例如在待分析的样本中的基因表达与控制水平相比相差(即，提高)例如5％、6％、7％、8％、9％、10％、15％、20％、25％、30％、40％、50％、或多于50％时，或者与控制水平相比相差至少0.1倍、至少0.2倍、至少1倍、至少2倍、至少5倍或至少10倍或更多倍时，将表达水平认为是“上调的”。所述控制水平可以是如在本文中上文所定义的正常控制水平或癌性控制水平。如果要进行与癌性控制水平的比较，则优选与正常控制水平的额外比较。这样的额外比较允许确定修改的趋势，例如，可以观测到表达水平增加的幅度和/或可以得出对应的结论。优选的是与良性前列腺癌或者与健康组织或者源于健康个体的样本进行比较。在本发明的上下文中，术语“下调的”或“下调的表达水平”或“表达水平的下降”(其可以同义地使用)因此表示在待分析的情况(例如，源自患者样本的情况)与参考点之间的表达水平的下降，所述参考点可以是能源自本领域技术人员已知的任何合适的前列腺癌或癌症阶段的正常控制水平或优选癌性控制水平。当例如在待分析的样本中的基因表达与控制水平相比相差(即，下降)例如5％、6％、7％、8％、9％、10％、15％、20％、25％、30％、40％、50％、或多于50％时，或者与控制水平相比相差至少0.1倍、至少0.2倍、至少1倍、至少2倍、至少5倍或至少10倍或更多倍时，将表达水平认为是“下调的”。所述控制水平可以是如在本文中上文所定义的正常控制水平或癌性控制水平。如果要执行与癌性控制水平的比较，则能够与正常控制水平进行额外比较。这样的额外比较允许确定修改的趋势，例如，可以观测到表达水平减少的幅度和/或可以得出对应的结论。优选的是与良性前列腺癌或者与健康组织或源于健康个体的样本进行比较。在本文中提到的(一个或多个)感兴趣基因的表达值能够被用于使用以下公式来建立“前列腺癌进展指数(pcpi)”：pcpi＝(gev_av_goi_up)-(gev_av_goi_down)，其中，goi指代所选择的感兴趣基因，例如，(生物)标记基因，与在初级处置之后有进展和没有进展的患者组之间上调的组相比，其被分组到在初级处置之后有进展和没有进展的患者组之间被下调的那些组中。计算针对下调基因的平均基因表达值(gev_av_goi_down)以及针对上调基因的平均基因表达值(gev_av_goi_up)。根据以下等式来计算对象样本特异性前列腺癌进展指数的具体实施例：pcpi＝(gev_av_goi_up)-(gev_av_goi_down)，其中gev_av_goi_up是上调基因的平均基因表达值，并且其中，gev_av_goi_down是下调基因的平均基因表达值，其中，所述值是基于每个患者样本的归一化基因表达数据来确定的，并且其中，“上调的基因”指代在初级处置之后在有进展或没有进展的患者组之间被上调的基因，而“下调的基因”指代在初级处置之后在有进展或没有进展的患者组之间被下调的基因。例如在图2中提供了对基因的选择，所述基因潜在地涉及前列腺癌中的患者分级，或者涉及确定在初级处置之后发展侵袭性前列腺癌的倾向。图2提供了被发现显著(p<0.05)不同地表达并且在相同方向(即，上调或下调)上的患者组之间调节的57个选定基因的概述。根据本发明的一个方面，这57个基因可以被用作goi。也能够使用从上述57个基因中选择的基因，例如，至少17个基因、至少18个基因、至少19个基因、至少20个基因、至少21个基因、至少22个基因、至少23个基因、至少24个基因、至少25个基因、至少26个基因、至少27个基因、至少28个基因、至少29个基因、至少30个基因、至少31个基因、至少32个基因、至少33个基因、至少34个基因、至少35个基因、至少36个基因、至少37个基因、至少38个基因、至少39个基因、至少40个基因、至少41个基因、至少42个基因、至少43个基因、至少44个基因、至少45个基因、至少46个基因、至少47个基因、至少48个基因、至少49个基因、至少50个基因、或者更多个基因。在另一方面中，提供了包括个体基因的组合的基因表达预后签名，其中，这些goi的表达水平能够使用例如以定量方式从人类前列腺癌组织样本中提取的rna来进行测量。这些特征组合到单个数据模型(即，pcpi)中提供了预测前列腺癌的进展的显著改善的分类能力。在一个优选实施例中，pcpi签名包括以下19个基因：pde4d5、pde4d7、azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2、col1a1、col3a1、col5a2、inhba、thbs2、vcan、bgn、birc5和dyrk2。术语“磷酸二酯酶4d5”或“pde4d5”涉及人类磷酸二酯酶pde4d的剪接变体5，即，人类磷酸二酯酶pde4d5基因，优选涉及在ncbi参考序列：nm_001197218.1中定义的序列，更优选涉及如在seqidno：1中阐述的核苷酸序列，其对应于上文所指示的pde4d5转录物的ncbi参考序列的序列，并且也涉及如在seqidno：2中阐述的对应氨基酸序列，其对应于在对pde4d5多肽进行编码的ncbi蛋白质加入参考序列np_001184147.1中定义的蛋白质序列。术语“磷酸二酯酶4d5”或“pde4d5”也涉及能够通过引物对pde1d5_正向(seqidno：3)和pde1d5_逆向(seqidno：4)生成的扩增子，并且能够通过探针seqidno：5来检测。术语“磷酸二酯酶4d7”或“pde4d7”涉及人类磷酸二酯酶pde4d的剪接变体7，即，人类磷酸二酯酶pde4d7基因，优选涉及在ncbi参考序列：nm_001165899.1中定义的序列，更优选涉及如在seqidno：6中阐述的核苷酸序列，其对应于上文所指示的pde4d7转录物的ncbi参考序列的序列，并且也涉及与如在seqidno：7中阐述的对应氨基酸序列，其对应于在对pde4d7多肽进行编码的ncbi蛋白质加入参考序列np_001159371.1中定义的蛋白质序列。术语“磷酸二酯酶4d7”或“pde4d7”也涉及能够通过引物对pde1d7_正向(seqidno：8)和pde1d7_反向(seqidno：9)生成的扩增子，并且能够通过探针seqidno：10来检测。术语“azgp1”涉及α-2-糖蛋白1-锌-结合基因，优选涉及如在ncbi参考序列：nm_001185.3中定义的序列，更优选涉及如在seqidno：11中阐述的核苷酸序列，其对应于上文所指示的azgp1转录物的ncbi参考序列的序列，并且也涉及如在seqidno：12中阐述的对应氨基酸序列，其对应于对azgp1多肽进行编码的ncbi蛋白质加入参考序列np_001176.1。术语“azgp1”也涉及能够通过引物对azgp1_正向(seqidno：13)和azgp1_逆向(seqidno：14)生成的扩增子，并且其能够通过探针seqidno：15来检测。术语“fbln1”涉及fibulin1基因，优选涉及如在ncbi参考序列：nm_001996.3、nm_006485.3、nm_006486.2和nm_006487.2中定义的序列中的一个或多个，更优选分别涉及在seqidno：16、17、18和19中阐述的核苷酸序列，其对应于上文所指示的fibulin1转录物的ncbi参考序列的序列，并且也涉及如在seqidno：20、21、22和23中阐述的对应氨基酸序列，其分别对应于在对fibulin1多肽进行编码的ncbi蛋白质加入参考序列np_001987.2、np_006476.2、np_006477.2和np_006478.2中定义的蛋白质序列。术语“fbln1”也涉及能够通过引物对fbln1_正向(seqidno：24)和fbln1_逆向(seqidno：250)生成的扩增子，并且能够通过探针seqidno：26来检测。术语“ilk”涉及整合素链接激酶基因，优选涉及如在ncbi参考序列：nm_001014794.2、nm_001014795.2、nm_001278441.1、nm_001278442.1和nm_004517.3中定义的序列中的一个或多个，更优选分别涉及如在seqidno：27、28、29、30和31中阐述的核苷酸序列，其对应于上文所指示的整合素链接激酶转录物的ncbi参考序列的序列，并且也涉及如在seqidno：32、33、34、35和36中阐述的对应氨基酸序列，其分别对应于在对整合素链接激酶多肽进行编码的ncbi蛋白质加入参考序列np_001014794.1、np_001014795.1、np_001265370.1、np_001265371.1和np_004508.1中定义的蛋白质序列。术语“ilk”也涉及能够通过引物对ilk_正向(seqidno：37)和ilk_逆向(seqidno：38)生成的(一个或多个)扩增子，并且能够通过探针seqidno：39来检测。术语“krt15”涉及角蛋白15基因，优选涉及如在ncbi参考序列：nm_002275.3中定义的序列，更优选涉及如在seqidno：40中阐述的核苷酸序列，其对应于上文所指示的krt15转录物的ncbi参考序列的序列，并且也涉及如在seqidno：41中阐述的对应氨基酸序列，其对应于在对krt15多肽进行编码的ncbi蛋白质加入参考序列np_002266.2中定义的蛋白质序列。术语“krt15”也涉及能够通过引物对krt15_正向(seqidno：42)和krt15_逆向(seqidno：43)生成的扩增子，并且能够通过探针seqidno：44来检测。术语“meis2”涉及meis同源异形体2，优选涉及如在ncbi参考序列：nm_001220482.1、nm_002399.3、nm_170674.4、nm_170675.4、nm_170676.4、nm_170677.4、nm_172315.2和nm_020149.2中定义的序列中的一个或多个，更优选分别涉及如在seqidno：45、46、47、48、49、50和/或51中阐述的核苷酸序列，其对应于上文所指示的meis2转录物的ncbi参考序列的序列，并且也涉及如在seqidno：53、54、55、56、57、58、59和/或60中阐述的对应氨基酸序列，其分别对应于在对meis2多肽进行编码的ncbi蛋白质加入参考序列np_001207411.1、np_002390.1、np_733774.1、np_733775.1、np_733776.1、np_733777.1、np_758526.1和np_758527.1中定义的蛋白质序列。术语“meis2”也涉及能够通过引物对meis2_正向(seqidno：61)和meis2_逆向(seqidno：62)生成的(一个或多个)扩增子，并且能够通过探针seqidno：63来检测。术语“mybpc1”涉及肌球蛋白结合蛋白c，慢型；优选涉及如在ncbi参考序列nm_001254718.1、nm_001254719.1、nm_001254720.1、nm_001254721.1、nm_001254722.1、nm_001254723.1、nm_002465.3、nm_206819.2、nm_206820.2和nm_206821.2中定义的序列中的一个或多个，更优选分别涉及在seqidno：64、65、66、67、68、69、70、71、72和/或73中阐述的核苷酸序列，其对应于上文所指示的mybpc1转录物的ncbi参考序列的序列，并且也涉及如在seqidno：74、75、76、77、78、79、80、81、82和/或83中阐述的对应氨基酸序列，其分别对应于在对mybpc1多肽进行编码的ncbi蛋白质加入参考序列np_001241647.1、np_001241648.1、np_001241649.1、np_001241650.1、np_001241651.1、np_001241652.1、np_002456.2、np_996555.1、np_996556.1和np_996557.1中定义的蛋白质序列。术语“mybpc1”也涉及能够通过引物对mybpc1_正向(seqidno：84)和mybpc1_逆向(seqidno：85)生成的(一个或多个)扩增子，并且能够通过探针seqidno：86来检测。术语“page4”涉及p抗原家族、成员4基因，优选涉及如在ncbi参考序列：nm_007003.3中定义的序列，更优选涉及如在seqidno：87中阐述的核苷酸序列，其对应于上文所指示的page4转录物的ncbi参考序列的序列，并且也涉及如在seqidno：88中阐述的对应氨基酸序列，其对应于在对page4多肽进行编码的ncbi蛋白质加入参考序列np_008934.1中定义的蛋白质序列。术语“page4”也涉及能够由引物对page4_正向(seqidno：89)和page4_逆向(seqidno：90)生成的扩增子，并且能够通过探针seqidno：91来检测。术语“srd5a2”涉及类固醇5-α还原酶2基因，优选涉及如在ncbi参考序列：nm_000348.3中定义的序列，更优选涉及如在seqidno：92中阐述的核苷酸序列，其对应于上文所指示的srd5a2转录物的ncbi参考序列的序列，并且也涉及如在seqidno：93中阐述的对应氨基酸序列，其对应于在对srd5a2多肽进行编码的ncbi蛋白质加入参考序列np_000339.2中定义的蛋白质序列。术语“srd5a2”也涉及能够通过引物对srd5a2_正向(seqidno：94)和srd5a2_逆向(seqidno：95)生成的扩增子，并且能够通过探针seqidno：96来检测。术语“col1a1”涉及胶原，i型，α1基因，优选涉及如在ncbi参考序列：nm_000088.3中定义的序列，更优选涉及如在seqidno：97中阐述的核苷酸序列，其对应于上文所指示的col1a1转录物的ncbi参考序列的序列，并且也涉及如在seqidno：98中阐述的对应氨基酸序列，其对应于在对col1a1多肽进行编码的ncbi蛋白质加入参考序列np_000079.2中定义的蛋白质序列。术语“col1a1”也涉及能够通过引物对col1a1_正向(seqidno：99)和col1a1_逆向(seqidno：100)生成的扩增子，并且能够通过探针seqidno：101来检测。术语“col3a1”涉及胶原，iii型，α1基因，优选涉及如在ncbi参考序列：nm_000090.3中定义的序列，更优选涉及如在seqidno：102中阐述的核苷酸序列，其对应于上文所指示的col3a1转录物的ncbi参考序列的序列，并且也涉及如在seqidno：103中阐述的对应氨基酸序列，其对应于在对col3a1多肽进行编码的ncbi蛋白质加入参考序列np_000081.1中定义的蛋白质序列。术语“col3a1”也涉及能够通过引物对col3a1_正向(seqidno：104)和col3a1_逆向(seqidno：105)生成的扩增子，并且能够通过探针seqidno：106来检测。术语“col5a2”涉及胶原，v型，α2基因，优选涉及如在ncbi参考序列：nm_000393.3中定义的序列，更优选涉及如在seqidno：107中阐述的核苷酸序列，其对应于上文所指示的col5a2转录物的ncbi参考序列的序列，并且也涉及如在seqidno：108中阐述的对应氨基酸序列，其对应于在对srd5a2多肽进行编码的ncbi蛋白质加入序列np_000384.2中定义的蛋白质序列。术语“col5a2”也涉及能够通过引物对col5a2_正向(seqidno：109)和col5a2_逆向(seqidno：110)生成的扩增子，并且能够通过探针seqidno：111来检测。术语“inhba”涉及抑制素，βa基因，优选涉及如在ncbi参考序列nm_002192.2中定义的序列，更优选涉及如在seqidno：112中阐述的核苷酸序列，其对应于上文所指示的inhba转录物的ncbi参考序列的序列，并且也涉及如在seqidno：113中阐述的对应氨基酸序列，其对应于在对inhba多肽进行编码的ncbi蛋白质加入参考序列np_002183.1中定义的蛋白质序列。术语“inhba”也涉及能够通过引物对inhba_正向(seqidno：114)和inhba_逆向(seqidno：115)生成的扩增器，并且能够通过探针seqidno：116来检测。术语“thbs2”涉及血小板反应蛋白2基因，优选涉及如在ncbi参考序列：nm_003247.3中定义的序列，更优选涉及如在seqidno：117中阐述的核苷酸序列，其对应于上文所指示的thbs2转录物的ncbi参考序列的序列，并且也涉及如在seqidno：118中阐述的对应氨基酸序列，其对应于在对thbs2多肽进行编码的ncbi蛋白质加入参考序列np_003238.2中定义的蛋白质序列。术语“thbs2”也涉及能够由引物对thbs2_正向(seqidno：119)和thbs2_逆向(seqidno：120)生成的扩增子，并且能够通过探针seqidno：121来检测。术语“vcan”涉及多功能蛋白聚糖基因，优选涉及如在ncbi参考序列：nm_001126336.2、nm_001164097.1、nm_001164098.1和nm_004385.4中定义的一个或多个序列，更优选分别涉及如在seqidno：122、123、124和125中阐述一个或多个核苷酸序列，其对应于上文所指示的vcan转录物的ncbi参考序列的序列，并且也涉及如在seqidno：126、127、128和129中阐述的对应氨基酸序列，其分别对应于在对vcan多肽进行编码的ncbi蛋白质加入参考序列np_001119808.1、np_001157569.1、np_001157570.1和np_004376.2中定义的蛋白质序列。术语“vcan”也涉及能够通过引物对vcan_正向(seqidno：130)和vcan_逆向(seqidno：131)生成的(一个或多个)扩增子，并且能够通过探针seqidno：132来检测。术语“bng”涉及双糖链蛋白多糖基因，优选涉及如在ncbi参考序列：nm_001711.4中定义的序列，更优选涉及如在seqidno：133中阐述的核苷酸序列，其对应于上文所指示的bng转录物的ncbi参考序列的序列，并且也涉及如在seqidno：134中阐述的对应氨基酸序列，其对应于在对bng多肽进行编码的ncbi蛋白质加入参考序列np_001702.1中定义的蛋白质序列。术语“bng”也涉及能够由引物对bng_正向(seqidno：135)和bng_逆向(seqidno：136)生成的扩增器，并且能够通过探针seqidno：137来检测。术语“birc5”涉及多功能蛋白聚糖基因，优选涉及如在ncbi参考序列：nm_001012270.1、nm_001012271.1和nm_001168.2中定义的一个或多个序列，更优选分别涉及如在seqidno：138、139和140中阐述的一个或多个核苷酸序列，其对应于上文所指示的birc5转录物的ncbi参考序列的序列，并且也涉及如在seqidno：141、142和143中阐述的对应氨基酸序列，其分别对应于在对birc5多肽进行编码的ncbi蛋白质加入参考序列np_001012270.1、np_001012271.1和np_001159.2中定义的蛋白质序列。术语“birc5”也涉及能够通过引物对birc5_正向(seqidno：144)和birc5_逆向(seqidno：145)生成的(一个或多个)扩增子，并且能够通过探针seqidno：146来检测。术语“dyrk2”涉及versican基因，优选涉及如在ncbi参考序列：nm_003583.3和nm_006482.2中定义的一个或多个序列，更优选分别涉及如在seqidno：147和148中阐述的一个或多个核苷酸序列，其对应于上文所指示的dyrk2转录物的ncbi参考序列的序列，并且也涉及如在seqidno：149和150中阐述的对应氨基酸序列，其分别对应于在对dyrk2多肽进行编码的ncbi蛋白质加入参考序列np_003574.1和np_006473.2中定义的蛋白质序列。术语“dyrk2”也涉及能够通过引物对dyrk2_正向(seqidno：151)和dyrk2_逆向(seqidno：152)生成的(一个或多个)扩增子，并且能够通过探针seqidno：153来检测。在其他实施例中，pcpi签名能够是包括pde4d而非pde4d5和pde4d7的18-基因列表，或者其可以包括剩余的17个基因。因此，在优选实施例中，pcpi签名能够是包括上文所提到的17个基因并且既不包括pde4d5也不包括pde4d7的17基因列表。在另一实施例中，本发明提供了基因表达预后签名，其包括19个个体基因的组合，所述个体基因能够以定量方式在来自人类前列腺癌组织样本的所提取的rna上进行测量。将这些特征组合成单数据模型(＝pcpi->前列腺癌进展指数)提供了显著改善的分类能力以预测前列腺癌的进展。在使用这19个基因或者17、18或57的实施例中，在本发明中提及的pcpi被用在诊断样本中的前列腺癌的方法中，预测患者的个体疾病状态以及预期的疾病发展，并且其在适用时提供用于针对个体优选的处置或疗法对患者进行分级和/或识别的方法中的参数。基于pcpi参数，能够确定例如肿瘤发展成侵袭性前列腺癌的倾向或可能性。例如，如果在对肿瘤的分析中获得的pcpi高于定义的截止(或阈值)水平，则所述肿瘤进展为侵袭性形式的概率也更高，并且反之亦然。根据在本文中所描述的方法而分析的肿瘤样本的分类步骤因此包括：在过去的特定时间点(例如，在初始诊断为前列腺癌之前)获得的样本以及在后续阶段处获得的样本之间的pcpi值的比较。当在所述后续阶段在对肿瘤样本的分析中获得的pcpi高于定义的阈值或截止值时，该参数能够被用作朝向侵袭性前列腺癌进展的指示。截止值可以基于包括具有或不具有进展的患者组的参考数据集来定义。对于没有或具有进展的患者的分类，可以将截止值设定为例如70％、80％、85％、90％、93％、95％、96％、97％、98％或99％的敏感性。在优选实施例中，所述截止值可以被设定为90％的敏感性。当然，pcpi也可以被用在建立患者预后的方法中，被用在用于将患者分级到组中以进行适当处置的方法中，借助于该方法，医师得出结论：特异性处置是不适当的，(尚且)不需要治疗，或者鉴于患者的总体身体状况而不再需要治疗。因此，本发明的实施例涉及识别和使用与前列腺癌临床相关的标记基因(或序列)表达模式(或“谱”或“签名”)。无论是在核酸表达、蛋白质表达还是其他表达格式中体现的标记基因表达谱都可以被用于预测罹患前列腺癌的对象的前列腺癌复发率和/或生存率。具体地，所述标记基因被用于建立在本文中所描述的用于识别/分类具有侵袭性或惰性疾病的患者的前列腺癌进展谱(pcpi)。在本申请的上下文中，表达“初始诊断”指代在执行根据本发明的方法之一的日期之前的第一次或随后的诊断，并且计算pcpi。例如，针对第一次并且优选在对前列腺癌的诊断之前分析其前列腺组织材料的患者，可以建立初始诊断。在本申请的上下文中，术语“在初始诊断之后的预定时段”包括大约6个月、1年、2年、3年、4年、5年、6年、7年、8年、9年、10年、15年或20年或更多年。在本申请的上下文中，表达“新近诊断有前列腺癌的患者”指代已经被诊断为具有确认或引起怀疑在从该患者第一次取得的样本中存在前列腺癌细胞的生化值、临床值或pcpi值的个体。在本申请的上下文中，表达“针对前列腺癌的初级处置”指代用于对前列腺癌的处置的任何已知方法，即，手术、化学疗法、利用生物制剂的处置、放射疗法等。在本申请的上下文中，表达“利用生物制剂的处置”指代利用单克隆抗体或者其衍生物，或者其肽或片段对前列腺癌的处置，其尤其抑制或阻断或中和涉及生长、增殖、维持的体内和体外生物学分子，或者前列腺癌细胞使用的任何其他代谢路径。针对所建立的靶标的单克隆抗体包括准许用于实体肿瘤的那些，诸如抗人egfr2单克隆抗体(诸如曲妥珠单抗)，抗egfr抗体(诸如利妥昔单抗和帕尼单抗)、以及抗血管内皮生长因子(vegf)单克隆抗体贝伐单抗。在本申请的上下文中，表达“生化复发”例如指代增加的psa的复发生物学值，其指示样本中的前列腺癌细胞的存在。然而，也能够使用能够被用于检测存在或引起怀疑这样的存在的其他标记。在本申请的上下文中，术语“临床复发”指代例如使用gleason分数测量的临床体征或临床值的存在。在本申请的上下文中，表达“易遭受疾病进展影响的前列腺癌的倾向”指代能测量的并且显著的参数(例如pcpi)，其提供了调查其样本的患者将发展侵袭性前列腺癌的可能性的指示，即，在对经诊断的前列腺癌的初级处置(例如，通过前列腺移除术、化学疗法和/或放射疗法)之后，前列腺癌细胞再次出现，其具有侵袭性生长的潜力，诸如在淋巴结和骨骼中形成转移。在本申请的上下文中，表达“用于确定患有前列腺癌的患者的预后的计算机实施的方法”指代以下方法，其中，软件算法计算pcpi并且基于此提供针对被分析的患者的预后，其中，该方法使用在测量在本文中所提及的基因的基因表达水平时获得的原始数据，并且使用上文所描述的方程将其转换成pcpi。在本申请的上下文中，以下方法，其用于对侵袭性前列腺癌的发展或进展的倾向的诊断、预后、识别，对患有前列腺癌或者在初级处置之后经受前列腺癌复发的患者的识别，可以基于根据本发明的方法中的任意方法获得的结果利用合适的治疗方案来进行处置。因此，例如，如果预后是基于确定针对这种类型的癌症的倾向的结果患者将发展侵袭性前列腺癌，那么医师可以决定是否使用可用疗法中的任意疗法来处置前列腺癌，诸如手术、化学疗法、放射疗法、激素疗法或者其组合等。根据本发明的方法也借助于pcpi来提供信息，基于pcpi能够决定患者是否应当进行手术、化学疗法、放射疗法，或者是否要执行进一步的活检。因此，pcpi表示建立个体化诊断、预后的重要参数，允许识别具有侵袭性前列腺癌倾向的患者，或者对其进行分级以用于最适合于该患者的疗法。pcpi也能够与其他手段和方法结合使用以建立诊断或预后，并且如在本文中所讨论地对患者进行识别或分级。因此，本发明也涉及如上文所指出的前列腺癌特异性疗法或处置，用于基于pcpi已经被识别为适合这样的疗法的患者的处置，任选地与其他诊断或预后方法相组合，以期为所述患者选择最合适的癌症处置。例如，当与控制样本相比pcpi较高时，对已经识别或诊断的患者或者已经使用本发明的方法建立预后的患者的处置中可以选择完全移除淋巴结。在涉及在初始临床诊断后通过前列腺移除术处置的患者的本发明的实施例中，本发明包括预测前列腺癌复发、癌症转移、和/或升高的psa水平的复发的可能性或倾向的方法。本发明的另外的实施例涉及识别并且然后使用在样本中的提供与前列腺癌有关的预后信息的标记基因(或序列)表达谱的方法。所述表达谱与具有良好或不良癌症复发率、癌症转移和/或生存结果的患者相关(并且因此能够在其之间进行区分)。在本发明的实施例中，提供了识别与患有前列腺癌患者的癌症复发和/或转移有关的标记基因表达谱的方法。在本发明的另外的实施例中，提供了以下方法，所述方法用于将在包括来自患者的前列腺癌细胞中的基因表达分析的样本中的标记基因(或序列)表达与所识别的表达谱(pcpi)进行比较，以确定例如在前列腺移除术、化学疗法、放射疗法等之后患者的可能结果。在本发明的这些实施例的另外的方面中，所获得的信息可以有利地被用于预测患者是否将可能从例如处置前列腺癌的手术中获益或者患者利用另一类型的处置是否将更好，或者是否需要除了手术之外的辅助处置。如在本文中所公开的，能够基于患者的前列腺样本的表达谱来选择可能从手术(诸如根治性前列腺移除术)获益的患者，从而在手术后没有癌症复发和/或转移。在另外的实施例中，可能预期不从手术获益的患者是通过如在本文中所公开的患者的前列腺癌细胞的表达谱预测在手术后发展癌转移的患者。通过范例的方式，前列腺癌的复发可以处在相同的位置，而转移经常到达不同的位置或组织，例如淋巴结或骨骼。本发明的另外的实施例涉及一种方法，所述方法从具有前列腺癌细胞的患者群体中或者在前列腺移除术之后，将患者识别为属于相对于另一亚群具有更好的癌症复发和/或生存结果的患者的亚群(诸如较低的复发或转移风险)，或者属于相对于另一亚群具有较差的癌症复发和/或生存结果(诸如复发或转移风险升高)的亚群。因此，本发明的方法允许将患者分级成亚群或亚型。本发明的方法涉及，任选在前列腺移除术后，通过针对在本文中所公开的pcpi进行测定而将具有前列腺癌的患者识别为可能具有更好或更差的癌症复发、癌症转移和/或生存结果的实施例。当对从患者获得的样本的先前主观解释(诸如基于免疫组织化学染色和主观分析)可能已经被用于确定侵袭性疾病相对于惰性疾病的倾向和/或处置前列腺癌患者，或者前列腺移除术前或术后的患者，或者已通过不同疗法处置的前列腺癌患者，本发明引入了反映表达模式的客观指标，其可以单独使用或者与其他(主观和/或客观)标准组合使用以提供对患者结果的更准确的评估，包括生存率以及癌症的复发或转移。因此，基于对本发明的标记基因表达模式的分析的方法包括用于检测/诊断前列腺癌或者前列腺癌移除术前或术后的预后的手段，或者更一般地，确定侵袭性或惰性疾病的初级处置前或初级处置后的倾向。pcpi基于对多于一种标记基因或表达的序列的分析，其能够区分前列腺癌阶段，或者以显著的准确性来区分前列腺移除术前或术后的前列腺癌阶段。(一个或多个)标记基因或表达的(一个或多个)感兴趣序列的(一个或多个)表达水平被识别为与结果相关，使得(一个或多个)表达水平与确定患者的优选处置协议相关。因此，本发明包括涉及任选地在前列腺移除术之前或之后，通过根据在本文中所公开的方法针对与患者结果相关的表达水平测定怀疑包含来自所述患者的癌细胞的前列腺样本，以确定罹患前列腺癌的对象的结果的方法的实施例。在本发明的另一实施例中，公开了一种用于确定对象患者中的前列腺癌复发和/或转移的风险的方法。在本发明的方法中，针对在本文中所公开的标记基因的表达水平，分析怀疑包括来自患者的前列腺癌细胞的样本。所述标记基因的合计表达水平能够与前列腺癌细胞群体中其(一个或多个)平均或中值表达水平进行比较。然后，该评估可以被用于确定在使用pcpi时从其获得样本的对象中前列腺癌复发和/或转移的风险。所公开的基因(或表达的序列)的表达水平与癌症复发和/或转移的低风险相关或者与癌症复发和/或转移的高风险相关。换言之，在本文中所公开的个体标记基因(或表达的序列)以较高或较低的水平(与前列腺癌细胞群体中的标准化表达值相比)表达，使得偏差与在先前诊断为前列腺癌的患者(任选为已经被专门处置前列腺癌的患者，或重新诊断的患者)中发生侵袭性与惰性癌症的更高或更低的风险或者倾向相关。在一些实施例中，针对表达水平进行测定可以通过使用选择的特别识别在本文中所公开的标记基因的核酸探针来执行。这些探针在合适的条件下杂交并检测如在本文中所公开的表达序列。在本发明的实施例中，探针能够被用于检测从表达的标记(基因)序列扩增的序列的区域。对标记(基因)序列的表达水平的检测或确定可以被称为检测或确定表达谱或签名。如在本文中所描述地识别和使用包括所公开的标记基因序列的本发明的表达模式。针对其识别，通过对mrna的表达水平进行量化来获得包含前列腺癌细胞的样本中基因表达水平的大采样。在一个实施例中，本发明包括通过分析来自单细胞或均质细胞群体的基因表达来检测标记基因(或序列)表达水平，所述单细胞或均质细胞群体已经此外可能通过简单的活检与污染细胞切离或者以其他方式被隔离或纯化。由于在来自不同患者的细胞之间以及在来自同一患者样本的细胞之间的众多基因的表达波动，因此将来自个体基因序列的表达的多个数据用作参考数据以生成模型，该模型继而允许识别个体基因和序列，所述个体基因和序列的表达与特定的前列腺癌、或者前列腺移除术前或术后的结果相关，或者其允许根据患者的侵袭性与惰性癌症的倾向对患者进行分类。在这些方法中，使用本申请的权利要求中和贯穿说明书中所提及的感兴趣标记基因，将基因表达水平优选转化为如上文所定义的pcpi。根据本发明，然后分析这些模型中的各种基因的标记基因表达水平，以识别核苷酸序列，所述核苷酸序列的表达与前列腺癌或前列腺癌处置后的结果正相关或负相关。本发明的优选实施例基于在细胞中对表达的标记基因序列的子集的识别，其被识别为与在本文中所描述的结果相关。本发明的表达模式或概况包括被转化成pcpi的这些识别的标记序列(或基因)的组合。使用多个样本用于识别表达的序列增加了基因被认为与前列腺癌复发、转移和/或生存结果相关的置信度。在没有足够的置信度的情况下，仍然不能预测特定基因是否实际上与结果相关，并且也不能预测基因的表达是否可以成功用于识别前列腺癌、或者前列腺移除术前或术后对象或患者的结果。可以选择与所公开的感兴趣的标记基因(或表达序列)相对应的所识别的核苷酸序列作为待检测或评估其预测属性的表达谱来进行评估。与一个结果相对于另一个高度相关的表达水平谱或pcpi可以被用于测定包含来自对象或患者的样本的前列腺癌细胞，以预测从其获得样本的对象的结果。这样的测定可以被用作基于所识别的结果来确定针对所述对象的治疗性处置的方法的一部分。这种相关性提供了如在本文中所公开的对前列腺癌复发、癌症转移和/或生存结果的分子确定。在不受理论束缚的情况下，并且提供以改善对本发明的理解，所公开的分子确定比涉及前列腺癌的其他分子指示器(例如，对前列腺血清抗原(psa)水平的确定)更有效。相关表达模式和谱的额外用途在于对细胞和组织的分类；对诊断和/或预后的确定；以及对疗法的确定和/或改变。区分的能力是通过将个体标记基因序列的表达识别为相关、而不是通过被用于确定实际表达水平的测定形式来赋予的。本发明的方法定量地或定性地反映“转录物”(基因组中基因的转录部分)中的(一个或多个)标记基因序列的表达。包含前列腺癌细胞的样本的性质不是限制性的，因为在所公开的方法中可以使用新鲜组织、新鲜冷冻组织和固定组织，诸如福尔马林固定的石蜡包埋(ffpe)组织。在一些实施例中，所述样本可以是针(芯)活检或其他活检的样本。为了检测所识别的表达模式或pcpi签名，本发明的实施例包括通过从已经与污染细胞切离或以其他方式被隔离或纯化(除此之外可能通过简单的活检)的单细胞或同质细胞群体中收集全局或接近全局的基因表达数据来检测基因(或序列)表达模式。然后，检测或者以其他方式测量模式或谱中标记基因(序列)的表达水平。在其他实施例中，一种方法可以仅检测或测量谱中的基因(序列)的表达水平，而不执行对其他基因或序列的表达的评估或其他确定。在额外的方面中，对表达水平的分析可以与前列腺癌的其他评估或指示器组合执行或者替代其进行。在一些实施例中，与确定在包括来自对象的前列腺癌细胞的样本中的前列腺癌等级的方法组合地进行所述分析。在其他实施例中，是与确定样本中前列腺癌阶段的方法进行组合。第三种可能性是与检测或确定对象中的psa水平进行组合，任选地在被用于隔离前列腺癌细胞的流程之前。当然，与这些代表性范例中的任何一个、两个或所有三个的组合是可能的。每当使用多于一种类型的评估时，结果都是多变量分析。本发明明确包括在本文中描述为多变量实施例的评估的所有可能的组合。通常，可以使用本领域技术人员已知的任何接受的评估前列腺癌等级和/或阶段的方法。在一些情况下，确定前列腺癌等级的方法包括确定gleason分数(或gleason分级)。在其他情况下，确定前列腺癌等级的方法包括根据美国癌症联合委员会(ajcc)的肿瘤分期系统来估计前列腺癌阶段。并且如在本文中所描述的，可以替代或组合gleason分数或ajcc肿瘤阶段确定来执行对基因(序列)表达水平的分析。在psa水平的情况下，可以在被用于提供包括前列腺癌细胞的样本的前列腺移除术之前进行其评估，以用于在本文中所描述的任何方法中使用。在其他实施例中，本发明包括用于检测在本文中所公开的基因(或序列)的表达的物理和方法学手段。这些手段可以涉及测定以下一个或多个方面：基于基因(或序列)的表达的dna模板、用作表达基因(或序列)的中间体的rna、或者由基因(或序列)表达的蛋白质产物。尽管本发明主要在人类前列腺癌的上下文中进行了描述，但是可以在已知可能患有前列腺癌的任何动物的前列腺癌的上下文中实践。用于应用本发明的动物的非限制性范例是哺乳动物，特别是那些对农业应用(诸如，但不限于：牛、羊、马和其他“农场动物”)重要的哺乳动物、前列腺癌的动物模型、以及人类陪伴的动物(诸如但不限于狗和猫)。基因表达“模式”或“谱”或“签名”以及对应的计算的pcpi指代在两种或更多种前列腺癌之间，或者前列腺移除术前或术后，癌症复发，转移和/或生存结果(其表达与能够区分结果相关)的感兴趣基因(表达序列)的相对表达。“基因”或“表达的序列”是以能检测的方式来编码和表达离散产物的多核苷酸，无论本质是rna还是蛋白质。应当领会到，多于一个的多核苷酸可以能够对离散产物进行编码。该项包括基因或表达序列的等位基因和多态性，其基于染色体位置以及在正常有丝分裂期间重组的能力对相同的产物、或者其功能相关的(包括功能的增益、减少或调制)类似物进行编码。术语“相关”或“相关性”或者其等价物指代在两个或更多个基因的表达与前列腺细胞的生理状态之间的关联，以排除如通过使用在本文中所描述的方法而识别的一个或多个其他状态。基因可以以更高或更低的水平来表达，并且仍然与一种或多种前列腺癌、或者前列腺癌移除术前或术后、状态或结果相关。如在本文中所使用的，在本发明的上下文中分析其表达的“标记基因”或“标记基因序列”也可以被描述为感兴趣基因(goi)。在本发明的实施例中，将给定的标记基因(或表达的序列)的表达强度标准化(例如，相对于以相对恒定水平表达的参考基因的表达，或者跨所有可用样本测量goi的表达，并且表达值被标准化)，以提供用于对标记基因表达签名(例如，pcpi)和其他参数(例如临床数据)的相关性分析的标准化值或分数。在许多情况下，所述表达数据被标准化，以中值为中心，并且如本领域技术人员在进一步使用之前已知地进行对数转换，例如在聚类和判别分析中。在使用多于一个表达水平的情况下(如在基因表达谱或指数的情况下，例如pcpi)，可以将所述值或分数相加，并且然后进行分析作为用于评估相关性或基于相关性进行分类的合计值。“多核苷酸”是任何长度的核苷酸(核糖核苷酸或脱氧核糖核苷酸)的聚合形式。该术语仅指代分子的初级结构。因此，该术语包括双链和单链dna和rna。其也包括已知类型的修饰，包括本领域已知的标签，甲基化，“帽”，利用类似物取代一个或多个天然存在的核苷酸，和核苷酸间修饰，诸如不带电荷的键(例如，硫代磷酸酯、二硫代磷酸酯等)，以及多核苷酸的未修饰形式。术语“扩增”在广义上被用于意指创建扩增产物能够利用dna或rna聚合酶酶促地制备。如在本文中所使用，“扩增”通常指代产生期望序列(特别是样本)的多个副本的过程。“多个副本”意指至少2个副本。“副本”不一定意指与模板序列完美的序列互补性或同一性。还能够使用本领域已知的任何测序方法来识别goi的序列。术语“对应的”在适当的情况下可以指代核酸分子与另一核酸分子共享大量的序列同一性。大量意指至少95％，通常至少98％，并且更通常至少99％，并且使用blast算法来确定序列同一性，如altschul等人在(1990)，j.mol.biol.215:403-410(使用公布的默认设置，即，参数w＝4，t＝17)所描述的。用于扩增mrna的方法通常是在本领域中已知的，并且包括逆转录物pcr(rt-pcr)，以及在美国专利申请序列号no.10/062857(2001年10月25日提交)和美国临时专利申请60/298847(2001年6月15日提交的)和60/257801(2000年12月22日提交的)中描述的那些，其全部内容通过引用被合并入本文，如同完全进行了阐述一样。可以使用的另一种方法是定量pcr(或q-pcr)。备选地，能够通过本领域已知的方法将rna直接标记为对应的cdna。术语“cq值”定义了在qrt-pcr(定量实时pcr)中的pcr循环，其中，所测量的荧光首次与背景荧光交叉。“微阵列”是离散区域的线性或二维阵列，每个离散区域具有限定的面积，形成在通常为固体支撑体(诸如，但不限于玻璃、塑料或合成膜)的表面上。微阵列上的离散区域的密度是由要在单个固相支撑体的表面上检测的固定化的多核苷酸的总数来确定的，诸如至少约50/cm2，至少约100/cm2，至少约500/cm2，但在一些实施例中低于约1000/cm2。所述阵列总共可以包含小于约500、约1000、约1500、约2000、约2500或者约3000个固定化的多核苷酸。如在本文中所使用的，dna微阵列是被放置在芯片或其他表面上的寡核苷酸或多核苷酸的阵列，所述芯片或其他表面被用于与来自样本的扩增或克隆的多核苷酸杂交。因为阵列中的多核苷酸的每个特定组的位置是已知的，所以样本多核苷酸的同一性能够基于它们与微阵列中的特定位置的结合来确定。因为本发明依赖于对过表达或欠表达的基因(或表达序列)的识别，本发明的一个实施例涉及通过将样本细胞的mrna或者其扩增或克隆的版本(诸如dna或cdna)与对特定基因序列唯一的多核苷酸进行杂交来确定表达。这种类型的多核苷酸可以包含未在其他基因序列中找到的基因序列的至少约20个、至少约22个、至少约24个、至少约26个、至少约28个、至少约30个或者至少约32个连续碱基对。如在前一句中所使用的术语“约”指代从所陈述的数值增加或减少1。其他实施例可以使用在其他基因序列中未发现的基因序列的至少或约50、至少或约100、至少约或150、至少或约200、至少或约250、至少或约300、至少或约350或者至少或约400个碱基对。在前面的句子中所使用的术语“约”指代从所陈述的数值增加或减少10％。这样的多核苷酸也可以被称为能够与在本文中所描述的基因序列或者其独特部分杂交的多核苷酸探针。在许多情况下，杂交条件是约30％v/v至约50％甲酰胺以及约0.01m至约0.15m杂交盐的严格条件，以及在约55℃至约65℃或更高的从约0.01m至约0.15m盐的洗涤条件，或者与其等同的条件。在其他实施例中，用于在本发明中使用的多核苷酸探针可以与应当确定其表达的标记基因序列具有约或95％，约或96％，约或97％，约或98％，或者约或99％的同一性。如上所述，使用blast算法来确定同一性。也可以基于如上所述在严格条件或者与其等同条件下用于本发明的方法的杂交表达的标记基因的能力来描述这些探针。在许多情况下，所述序列是由标记基因编码的mrna，与这样的mrna相对应的cdna，和/或这样的序列的扩增版本。在本发明的一些实施例中，将多核苷酸探针在阵列、其他设备上或者固定在定位探针的个体斑点中。能够根据本发明使用的合适的标签包括放射性同位素、核苷酸发色团、酶、底物、荧光分子、化学发光基团、磁性颗粒、生物发光基团等。这样，标签是通过光谱、光化学、生物化学、免疫化学、电学、光学或化学手段能检测的任何复合物。术语“支撑体”指代常规的支撑体，诸如珠粒、颗粒、浸渍棒、纤维、过滤器、膜和硅烷或硅酸盐支撑体(诸如玻璃载片)。如在本文中所使用的，“前列腺组织样本”或“前列腺癌细胞样本”指代从个体(诸如患有前列腺癌的个体)隔离的前列腺组织的样本。所述样本可以来自经由前列腺移除术(诸如根治性前列腺移除术)移除的材料。备选地，能通过其他手段获得它们，诸如针状(芯)活检或其他活检技术，如侧向活检，常规的六分仪活检方法，作为扩展技术的六分仪和侧向活检的不同组合，经直肠超声引导的前列腺活检，以及其他如本领域技术人员已知的技术。这样的样本是初级隔离物(与培养的细胞相反)，并且可以通过本领域公认的任何合适的手段来收集。在一些实施例中，“样本”可以通过侵入性方法来收集，包括但不限于手术活检。样本可以包含前列腺癌细胞，通过已知方法或熟练从业者认为需要的其他适当方法对其进行隔离。在根据本发明使用之前，隔离方法包括但不限于显微切割、激光捕获显微切割(lcm)、或者激光显微切割(lmd)。“表达”和“基因表达”包括核酸材料的转录和/或翻译。如在本文中所使用的，术语“包括”及其同源词以其包括的含义使用；亦即，相当于术语“包括”以及其对应的同源词。“允许”事件发生的条件或者“适合于”发生事件(诸如杂交、链延伸等)的条件或“适合的”条件是不妨碍这样的事件发生的条件。因此，这些条件允许、增强、促进和/或有利于所述事件。本领域已知并且如在本文中所描述的这样的条件取决于例如核苷酸序列的性质、温度和缓冲条件。这些条件也取决于期望的事件，诸如杂交、切割、链延伸或转录。“检测”包括任何检测手段，包括对基因表达以及其中的改变的直接和间接检测。例如，可以直接或间接观测“可检测性较低”的产物，并且该术语指示任何减少(包括不存在能检测的信号)。类似地，“可检测性较高”产物意指任何增加，无论是直接还是间接地观测到。“前列腺移除术”指代由熟练的临床医师(诸如外科医师)对前列腺组织的移除。非限制性范例包括根治性前列腺移除术；开放(常规)前列腺移除术(涉及通过会阴切口)；腹腔镜前列腺移除术；以及机器人(保留神经)前列腺移除术。“gleason分数”指代根据gleason系统由经训练的病理学家对前列腺癌的样本进行分级，gleason系统基于前列腺组织的样本的细胞中与癌组织或正常前列腺组织的相似性，使用1至5的数字来分配gleason分数。对看起来非常像正常前列腺组织的组织给予分数或等级1，而对缺乏正常特征的组织以及似乎随意地通过前列腺散布的细胞给予分数或等级5。分数或等级2到4(包含)具有在这些可能性之间的特征。但是，因为前列腺癌可能包括具有不同分数或等级的区域，所以对组成大部分组织的两个区域给出单独的分数或等级。将所述两个分数或等级相加以产生在2至10之间的gleason分数(或者gleason之和)。在本文中所提及的标记基因的表达水平与在本文中所描述的临床结果相关，并且因此可以被用作如在本文中所描述的预测子。已经报道了所识别的基因将参与如http://csbi.ltdk.helsinki.fi/anduril/tcga-gbm/table4_2.html中概述的各种细胞功能。在本发明实施例下的方法中，如在wo2010131194和wo2010131195(其内容通过引用并入本文)中所描述的，这些数据与推定的预后基因标记pde4d7相关。在本发明的背景下，选择显示出显著相关性的那些分子路径用于下游分析(图2)。在本发明的实施例中，标记基因表达模式(或pcpi)可以与术前或术后psa水平、gleason分数和pt阶段相关。所述谱也能够将具有gleason分数<＝6和7的样本分级为psa失败的低风险和高风险。在具有已知预后因子的多变量分析中，谱是保持统计学显著性的仅有的预测子(p<0.05)。因此，在活检中或者在前列腺移除术期间移除的组织中对谱的检测允许区分惰性癌症和侵袭性癌症。因此，本发明的实施例涉及识别和使用在对象中区分(或相关)前列腺癌生存和复发结果的基因表达模式(或谱或“签名”)。这样的模式可以通过本发明的方法通过使用许多参考细胞或组织样本来确定，诸如由前列腺癌的病理学中的普通病理学家回顾的那些，其反映前列腺癌细胞而不是正常的或其他非癌细胞。其样本可以与表达数据相关的对象经历的结果，以识别与结果相关的模式。因为总体基因表达谱因人、癌症以及癌症细胞而异，因此可以如在本文中所公开的那样进行在特定细胞与表达或欠表达的基因之间的相关性，以识别能够区分前列腺癌结果的基因。在本发明的实施例中，使用与前列腺癌(或前列腺移除术前或术后)生存、转移或复发结果显著相关的基因来区分结果。模式或指数能够基于用于模型中进行区分的基因的表达来预测对未知样本的分类。在本发明的实施例中，与前列腺癌、或者前列腺移除术前或术后/初级处置结果相关地表达的标记基因(序列)提供了将基因表达分析仅聚焦于有助于在不同结果中对对象进行分级的能力的那些基因。如本领域技术人员将领会的，表达模式(和pcpi)对于区分前列腺癌、或者前列腺移除术前或术后中的不同结果是非常有用的，并且本领域技术人员可以容易地执行以允许生成如上文所描述的模型，从而基于这些基因的表达水平来预测未知样本的状态。为了确定在本发明的实践中的基因(表达序列)的(上调的或下调的)表达水平，可以使用本领域已知的任何方法。在一些实施例中，使用基于对与在本文中识别并且公开的基因(或探针序列)杂交的rna的检测的表达。这很容易通过本领域已知的或公认为等同的任何rna检测或扩增+检测方法来执行，诸如但不限于rna测序、逆转录-pcr(rt-pcr)、实时pcr，实时rt-pcr、在美国专利申请系列号no.10/062857(2001年10月25日提交)以及美国临时专利申请60/298847(2001年6月15日提交)和60/257801(2000年12月22日提交)中公开的方法，以及用于检测存在或不存在rna稳定化或去稳定化序列的方法。备选地，可以使用基于对dna状态的检测的表达。将所识别的基因的dna检测为甲基化或删除的可以用于具有与特定前列腺癌、前列腺移除术前或术后、结果相关的表达降低的基因。这可以通过本领域已知的基于pcr的方法容易地执行，包括但不限于q-pcr。相反地，将所识别的基因的dna检测为扩增的可以用于具有与特定的前列腺癌、前列腺移除术前或术后、结果相关的上调表达的基因。这可以通过本领域已知的基于pcr的荧光原位杂交(fish)和染色体原位杂交(cish)方法容易地执行。例如，除了计算针对个体样本/患者的pcpi之外，也可以使用基于检测蛋白质水平或活性的存在、增加或减少的表达。可以通过本领域已知的基于任何免疫组织化学(ihc)、基于血液(特别是针对分泌的蛋白质)、基于抗体(包括抗蛋白质的自身抗体)、基于剥离细胞(来自癌症的)、基于质谱、以及基于图像(包括使用标记的配体)的方法，并且所述方法被认为适合于检测蛋白质。基于抗体和基于图像的方法额外地能用于通过使用通过非侵入性流程(诸如灌洗或针抽吸)获得的细胞来确定癌症之后的肿瘤的定位，其中，癌细胞的来源是未知的。标记的抗体或配体可以被用于定位患者体内的(一处或多处)癌变。涉及使用基于核酸的测定来确定表达的本发明的实施例通过将在本文中所识别的标记基因的一个或多个序列固定为固体支撑体上的多核苷酸来完成，所述固体支撑体包括但不限于固体基质，如本领域已知的阵列或基于珠粒的技术。在一些实施例中，所述测定是能从illumina获得的dasl(cdna介导的退火、选择、延伸和结扎)测定。备选地，也可以使用本领域已知的基于溶液的表达测定法。固定的多核苷酸探针对于所公开的基因(或表达的序列)可以是独有的或者以其他方式特异性的，使得多核苷酸能够与对应于基因(或表达的序列)的dna或rna杂交。这些多核苷酸可以是基因(或表达的序列)的全长或者是较短长度的探针(通过从序列的5'或3'端删除，比本领域已知的全长序列短达一个核苷酸)，其任选地是最小地中断的(诸如通过错配或插入非互补碱基对)，从而其与对应于基因(或表达的序列)的同源dna或rna的杂交不受影响。在许多实施例中，多核苷酸探针包含来自所公开的基因或表达的序列的3'端的序列。也可以使用包含相对于所公开基因的序列的突变的多核苷酸探针，只要突变的存在仍然允许杂交以产生能检测的信号即可。固定化的多核苷酸可以被用于确定由(一个或多个)样本前列腺细胞制备的核酸样本的状态，针对所述样本前列腺细胞，样本的对象(例如，从其获得样本的患者)的结果是未知的，或者确认已经被分配到样本对象的结果。在不限制本发明的情况下，这样的细胞可以来自患有前列腺癌的患者，诸如通过前列腺移除术移除的材料。(一个或多个)固定化的多核苷酸只需要足以在合适的条件下与源自样本的对应核酸分子进行特定的杂交。尽管甚至单个相关的基因的表达可以能够在区分两种前列腺癌结果时提供足够的准确度，但是本发明包括使用来自多于一种基因或表达序列的表达水平。具体地，使用实施例部分(下文)中提到的17、18、19的组或57的组的基因(表达序列)。在一些实施例中，可以通过使用适当的引物(诸如在pcr中使用的)来优先扩增源自(一个或多个)样本前列腺癌细胞的核酸，从而仅扩增待分析的基因以减少来自样本中的其他表达的基因或序列的污染背景信号。本发明的pcr扩增的大小可以是任意大小，包括至少或约50、至少或约100、至少约或150、至少或约200、至少或约250、至少或约300、至少或约350、或者至少或约400个连续的核苷酸，全都包括与所使用的pcr引物互补的部分。当然，pcr任选地可以是逆转录耦合pcr(或者在rna起始材料的情况下是rt-pcr)或定量pcr，诸如实时pcr，或者其组合。当然，来自在本文中所描述的样本的rna可以通过本领域技术人员容易知晓的手段来制备和使用。备选地，并且在要分析多个基因或者使用非常少的细胞(或一个细胞)的情况下，来自样本的核酸可以在与固定化的多核苷酸探针杂交之前被全局地扩增，诸如在阵列或微阵列上。当然，rna或其cdna对应物可以通过本领域中已知的方法直接标记和使用，而无需扩增。用于检测在本文中所描述的标记基因的方法的优选实施例是rna测序。本发明提供了一组更为客观的标准，以离散的一组标记基因的基因表达谱的形式，来区分(或描绘)前列腺癌、或者前列腺移除术前或术后、结果，并且允许预测针对侵袭性与惰性疾病的倾向。在一些实施例中，所述测定被用于在约6个月、1年、2年、3年、4年、5年、7年、10年、15年或甚至更晚的时间内区分更好和更差的结果。尽管更好和更差的癌症复发、转移和/或生存结果可以相比于彼此进行相对地定义，但是可以将“更好”的结果或“良好预后”看作在手术介入以移除(一个或多个)前列腺癌症肿瘤后约60个月之后比50％癌症复发几率和/或50％生存几率更好的结果。“更好的”结果或者“良好的预后”也可以是在手术介入后约60个月的优于约60％、约70％、约80％或约90％的癌症复发和/或生存几率。“更差”的结果/预后可以被视为在手术介入以移除(一个或多个)前列腺癌肿瘤的约60个月之后的50％或更大癌症复发几率和/或低于50％的生存几率。pcpi和根据本发明的方法帮助将患者分类成具有上述预后的患者。所公开的方法也可以与固体组织材料一起使用。例如，可以收集固体活检并进行制备以用于可视化，然后确定在本文中所识别的两个或更多个基因或表达的序列的表达以确定前列腺癌、或者前列腺移除术前或术后、结果。一种手段是通过使用与(一个或多个)多核苷酸识别探针进行原位杂交以用于测定(一个或多个)所述基因的表达。在一些实施例中，为了方便和准确，对来自样本的基因表达的检测可以通过使用能够测定来自本文中所公开的一些或所有基因的基因表达的单个微阵列。本发明的其他用途包括提供识别如与特定的前列腺癌生存或复发结果相关的前列腺癌细胞样本以用于进一步研究或学习的能力。这在需要基于客观的基因或分子标准来识别细胞的许多情况下提供了特别的优点。用于在本发明的方法中使用的材料理想地适用于制备按照公知方法生产的套件。本发明因此提供了包括用于对所公开的用于识别前列腺癌、或前列腺移除术前或术后、结果的基因的表达和序列的表达的检测的试剂的套件。这样的套件任选包括提供具有与其在本发明的方法中的用途相关的识别描述或标签或指令的试剂。这样的套件可以包括容器，每个容器具有在所述方法中使用的各种试剂(通常为浓缩形式)中的一种或多种，例如包括预制微阵列、缓冲器、合适的三磷酸核苷酸(例如，datp、dctp、dgtp和dttp；或ratp、rctp、rgtp和utp)、逆转录酶、dna聚合酶、rna聚合酶以及本发明的一种或多种引物复合物(例如，适合长度的多聚(t)或链接到与rna聚合酶反应的启动子的随机引物)。通常也将包括一组指令。本发明所提供的方法也可以全部或部分自动化。本发明的所有方面也可以被实践为使得其基本上包括所公开基因的子集，排除与经由包含细胞的样本对前列腺癌复发、转移和/或生存结果的识别无关的材料。在本发明的方法的上下文中，pcpi被用于诊断患者的前列腺癌，识别患者的前列腺癌，并建立前列腺癌患者的预后，确定发展侵袭性与惰性疾病的倾向性，并且对前列腺癌患者进行分级，从而处置医师能够(如果发生的话)决定应当如何处置患者。pcpi能够被用作上述目的的唯一参数，或者其能够与其他已知的诊断、预后或分级方法组合使用从而为医师提供进一步的支持。如在本文中所使用的，术语“诊断前列腺癌”意指，与在本文中上文所定义的控制水平相比，优选如果与在本文中上文所定义的正常控制水平相比，当本发明的goi的表达水平被上调或下调，pcpi显著高于/不同于在控制组织中发现的水平时，则患者或个体可以被认为患有前列腺癌。术语“诊断”也指代通过所述比较过程得出的结论。在本发明的另一实施例中，所述诊断可以与另外的癌症生物标记表达水平的阐述相结合，特别是前列腺癌生物标记。本领域技术人员将知道若干种特定的前列腺癌生物标记。例如，可以测试生物标记(如psa)的表达。当与在本文中上文所定义的正常控制水平相比本发明的goi的表达水平被上调或下调时并且当pcpi显著高于利用控制材料获得的pcpi时，可以认为诊断出前列腺癌。在另外的优选实施例中，如果在本文中所提到的goi的表达水平被上调或下调的值在20％至80％之间，优选在与控制水平(优选为标准化控制水平)相比较时在测试样本中的30％、40％、50％、60％或70％的值，则可以认为诊断出前列腺癌或者确定了发展侵袭性与惰性疾病的倾向。如在本文中上文所定义的，所述控制水平可以是正常控制水平或癌症控制水平。在特别优选的实施例中，如果如在本文中上文所定义的表达水平被上调或下调了1.5至10倍的因子，优选与控制水平相比较在测试样本中2至5倍的因子，特别是在健康组织或良性前列腺癌中或者非常优选地与初始诊断时相同患者的前列腺癌组织中，则可以认为诊断出前列腺癌或发展侵袭性与惰性疾病的倾向。如在本文所使用的术语“检测前列腺癌”意指可以确定有机体中前列腺癌疾病或失调的存在或者可以在有机体中识别出这样的疾病或失调。对前列腺癌疾病或失调的确定或识别可以通过比较本发明的goi的表达水平与在上文定义的正常控制水平或者通过确定pcpi来完成。与在本文中上文所定义的正常控制水平相比较，当goi的表达水平被上调或下调时，可以检测到前列腺癌。在本发明的优选实施例中，如果goi的表达水平与已建立的(例如，独立建立的)前列腺癌细胞或细胞系(例如，前列腺奥细胞系或上述细胞系)的表达水平相似，则可以检测到前列腺癌。如在本文中所使用的，术语“监视前列腺癌”和“识别具有易疾病进展的前列腺癌的倾向的对象”(即，识别侵袭性疾病与惰性疾病)涉及例如在处置流程期间或之后或者在特定时段期间或之后伴随所诊断或检测到的前列腺癌疾病或失调，通常在2个月、3个月、4个月、6个月、1年、2年、3年、5年、10年，或者在初级处置的开始和结束期间或之后的任何其他时段。术语“伴随”意指，如在本文中上文所定义的疾病状态或pcpi，并且特别是这些疾病状态或pcpi的变化，可以通过以下操作来检测：将样本中本发明的goi的表达水平与在本文中上文所定义的正常控制水平(优选源自良性肿瘤控制或健康控制的控制表达水平)进行比较，或者与建立的(例如独立建立的)前列腺癌细胞或细胞系(例如，前列腺癌细胞系或任何类型的周期性时间分段中的细胞系)的表达水平进行比较，所述周期性时间分段例如是：每周，每2周，每月，每2、3、4、5、6、7、8、9、10、11或12个月，每1.5年，每2、3、4、5、6、7、8、9或10年，在任何时间段期间，例如，分别在2周，3周，1、2、3、4、5、6、7、8、9、10、11、12个月、1.5、2、3、4、5、6、7、8、9、10、15或20年。所建立的(例如，独立建立的)产生额外的控制水平的前列腺癌细胞或细胞系可以来源于与癌症发展的不同阶段相对应的样本，例如，tnm分类系统的阶段0和i至iv。在本发明的优选实施例中，该术语涉及对所诊断的前列腺癌的伴随，例如，恶性激素敏感的前列腺癌。所述监测也可以包括对额外基因或基因元素的表达的检测，例如，看家基因，如gapdh或pbgd。本发明也涉及监测患者的方法，以使用整个说明书中公开的pcpi来识别在本文中所公开的签名基因中的变化，以便识别那些可能发展侵袭性前列腺癌的患者。然后，这些患者将按照整个说明书中所描述地进行治疗。如在本文中所使用的，术语“预测(侵袭性)前列腺癌”指代例如在处置期间或者在治疗之后，在特定时间段期间，预测所诊断或检测到的侵袭性前列腺癌的过程或结果。该术语也指代确定从疾病生存或恢复的机会，以及指代预测患者的预期生存时间。预后具体可以涉及在未来的一段时间期间建立患者生存的可能性，诸如6个月、1年、2年、3年、5年、10年或任何其他时间段。如在本文中所使用的，术语“朝向前列腺癌的进展”和“朝向侵袭性(与惰性)前列腺癌的进展”涉及在癌症发展的不同阶段之间的切换，例如，tnm分类的阶段0以及i至iv，或者任何其他阶段或亚阶段，从健康状况直至恶性激素敏感性或恶性激素抵抗性前列腺癌。通常，与来自同一个体的先前测试样本相比，例如，与来源于良性前列腺癌控制或健康组织控制的样本相比，在测试样本中，这样的切换伴随有对(一个或多个)标记基因或goi的表达水平以及如在本文中所使用的不同pcpi的修改。如果如在本文中上文所定义的用于计算pcpi的goi的表达水平不同，例如，在与来自同一个体的测试样本中从基因表达值计算的先前pcpi相比，在测试样本中，不同的值在3％至50％之间，优选不同的值为10％、15％、20％或25％，则可以认为检测到或诊断出朝向侵袭性前列腺癌的进展。可以在任何时间段检测修改，优选在1、2、3、4、5、6、7、8、9、10、11、12个月、1.5、2、3、4、5、6、7、8、9、10、15或20年期间，即，上文所指出的值可用通过对在上文所指示的时间段之后的第一时间点和第二时间点处的(一个或多个)标记基因或goi的表达水平或者pcpi来计算。在本发明的特别优选的实施例中，术语“朝向前列腺癌发展”涉及从健康状态或良性前列腺癌状态切换到恶性前列腺癌状态。与来自被诊断为健康的同一个体的先前测试样本相比，在测试样本中，如果如在本文中上文所定义的pcpi高出20％至50％之间的值，优选高出20％、25％、30％或35％的值，则可以认为检测到或诊断出从健康状态到前列腺癌状态的进展。备选地，为了比较，可以使用来自其他个体的测试样本，例如，健康个体的测试样本。也设想到了使用关于表达的可用数据库信息或采用癌细胞收集样本等。与来自已经被诊断为患有良性前列腺癌的同一个体的先前测试样本相比，在测试样本中，如果如在本文中上文所定义的pcpi高出3％至30％之间的值，优选高出5％、10％、15％或20％的值，则认为检测到或诊断出从良性前列腺癌状态进展至恶性前列腺癌状态。备选地，为了进行比较，可以使用来自其他个体的测试样本，例如，被诊断为患有良性前列腺癌的个体的测试样本。也设想到了使用关于表达的可用数据库信息或采用癌细胞采集样本等。可以在任何时间段检测修改，优选在1、2、3、4、5、6、7、8、9、10、11、12个月、1.5、2、3、4、5、6、7、8、9、10、15或20年，即，上述值能够通过比较在上述时段之后的第一时间点和第二时间点标记基因或goi的表达水平来计算。在本发明的另一实施例中，涉及诊断和检测发展前列腺癌的倾向。在本发明的上下文中，“发展(侵袭性)前列腺癌的倾向”是发展(侵袭性)前列腺癌的风险状态。优选地，在其中本文上述定义的goi的表达水平或pcpi与本文定义的控制水平显著不同的情况下，可以存在发展侵袭性前列腺癌的倾向，所述控制水平即来源于明显健康的患者的组织或样本或者来源于在初始诊断前列腺癌之前获得的患者的样本或组织的参考表达水平或参考pcpi，从而基于癌组织中的基因表达计算出的pcpi也高于从控制样本获得的pcpi。因此，如果观测到上述情况，则认为诊断出或检测到侵袭性前列腺癌的倾向。通常，并且也在建立pcpi时，能够将在测试生物学样本的表达水平与控制水平之间的差异标准化为另外的控制核酸的表达水平，所述另外的控制核酸例如是持家基因，其表达水平已知不会根据细胞的癌性或非癌性状态而不同。示范性控制基因尤其包括β-肌动蛋白、甘油醛-3-磷酸脱氢酶(gapdh)、胆色素原脱氨酶(pbgd)等。在本发明的上下文中，术语“诊断”和“预测”也意图涵盖预测和可能性分析。作为参数的pcpi因此可以在临床上用于作出关于治疗模式的决定，包括治疗性介入或诊断标准，诸如针对疾病的监管。根据本发明，可以提供用于检查患者状况的中间结果。这样的中间结果可以与额外信息相组合以辅助医生、护士或其他从业者诊断患者患有疾病。备选地，本发明可以被用于检测来源于患者的组织中的癌细胞，并且向医生提供有用的信息以诊断患者患有该疾病。根据本发明要被诊断、监测或者在其中要检测或预测前列腺癌、朝向侵袭性与惰性前列腺癌的进展或者针对侵袭性与惰性前列腺癌的倾向的患者或个体是动物，优选是哺乳动物，更优选是人类。除了pcpi作为用于诊断、检测、监测或预测朝向侵袭性与惰性前列腺癌的进展的前列腺癌的标记之外，使用如本领域技术人员已知的分子成像工具，例如，磁共振成像(mri)和/或磁光子共振成像(mpi)技术和/或多参数mri(mpmri)技术。在另一方面中，本发明涉及用于在个体中诊断、检测、监测或预测前列腺癌或朝向前列腺癌的进展或前列腺癌的倾向的复合物。根据本发明的复合物可以包括(一种或多种)goi表达产物的核酸亲和配体。如在本文中所使用的，术语“用于goi表达产物的核酸亲和配体”指代能够与goi转录物特异性结合的核酸分子。所述核酸亲和配体也可以能够与至少90％、91％、92％、93％、94％、95％、96％、97％、98％或99％等同于goi序列或所述序列的任何片段的核酸序列特异性结合。如在本文中所使用的，术语“表达产物”指代由goi的表达所生成的goi或mrna分子的转录物。更优选地，该术语涉及如上文所定义的经处理的转录物。本发明的复合物例如可以包括针对goi表达产物特异性的一组寡核苷酸和/或针对goi表达产物特异性的探针。如在本文中所使用的，术语“针对goi表达产物特异性的寡核苷酸”指代与goi的有义链或反义链互补的核苷酸序列。所述寡核苷酸可以具有本领域技术人员已知的任何合适的长度和序列，如能从goi或其互补序列得到的。通常，所述寡核苷酸可以具有在8至60个核苷酸之间的长度，优选在10至35个核苷酸之间的长度，更优选是11、12、13、14、15、16、17、18、19、20、21，22、23、24、25、26、27、28、29、30、31、32或33个核苷酸的长度。寡核苷酸序列，例如，可用作针对goi表达产物特异性的正向和反向引物的寡核苷酸，可以借助于本领域技术人员已知的软件工具来定义。如在本文中所使用的，术语“针对goi表达产物特异性的探针”意指与在本文中所描述的goi的有义链或反义链互补的核苷酸序列。所述探针可以具有本领域技术人员已知的任何合适的长度和序列，如能从在本文中所描述的goi的序列得到的。通常，所述探针可以具有在6至300个核苷酸之间的长度，优选在15至60个核苷酸之间的长度，更优选是20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、49或50个核苷酸的长度。可以在本领域技术人员已知的软件工具的帮助下来定义针对goi表达产物特异性的探针序列。如在本文中上文所描述的核酸亲和配体可以利用各种标记进行标记，或者可以通过利用各种标记进行标记的次级亲和配体来检测，以允许检测、可视化和/或量化。这能够通过使用任何合适的标签来实现，所述标签能够使用本领域技术人员已知的任何合适的技术或方法缀合(conjegate)至能够与表达产物交互的亲和配体或者缀合至任何次级亲和配体。术语“次级亲和配体”指代能够结合到如在本文中上文所定义的亲和配体的分子(即，如果在具有两个交互的亲和配体的系统中使用的情况下，则为“初级亲和配体”)。结合交互优选是特定结合。能够缀合到初级和/或次级亲和配体的标签的范例包括荧光染料或金属(例如，荧光素、若丹明、藻红蛋白、荧光胺)，发色染料(例如，视紫红质)、化学发光化合物(例如，鲁米那、咪唑)以及生物发光蛋白质(例如，荧光素、萤光素酶)、半抗原(例如生物素)。在本发明的实施例中，要被用作探针的核酸亲和配体，特别是在本文中上文所定义的针对goi表达产物特异性的探针，可以利用荧光标签(如6-fam、hex、tet、rox、cy3、cy5、德克萨斯红或罗丹明)和/或同时利用与淬灭标签(如tamra、dabcyl、黑洞猝灭剂、bhq-i或bhq-2)进行标记。在stryer，1968，science，162:526-533中描述了各种其他有用的荧光剂和发色团。亲和配体也可以利用酶(例如，辣根过氧化物酶、碱性磷酸酶、β-内酰胺酶)、放射性同位素(例如，3h、14c、32p、33p、35s、125i)或颗粒(例如，金)进行标记。可以使用各种化学方法(例如，胺反应或硫醇反应)将不同类型的标签缀合至亲和配体。然而，也可以使用除胺和硫醇之外的其他反应性基，例如醛、羧酸和谷氨酰胺。在本发明的特定实施例中，复合物可额外地包括辅助成分，如pcr缓冲剂、dntp、聚合酶、离子(如二价阳离子或单价阳离子)、杂交溶液、检测染料以及任何其他适合的化合物或液体，其对于执行如本文上面所定义的检测是必需的，这对本领域技术人员是已知的。在另一方面中，本发明涉及针对goi表达产物使用核酸，如在本文中上文所定义的，用于制备用于诊断、检测、监测或预测在个体中的前列腺癌或朝向侵袭性与惰性前列腺癌的进展或侵袭性与惰性疾病的倾向的复合物，如在本文在上文所描述的。在优选实施例中，本发明涉及使用针对goi表达产物特异性的一组寡核苷酸和/或针对表达产物特异性的探针，如在本文中上文所定义的，用于制备用于在个体中诊断、检测、监测或预测前列腺癌或朝向侵袭性与惰性前列腺癌的进展或侵袭性与惰性疾病的倾向的复合物，如在本文在上文所描述的。在本发明的优选实施例中，如在本文中上文所定义的复合物是诊断复合物。在另一方面中，本发明涉及用于检测、诊断、监测或预测前列腺癌或朝向前列腺癌的进展或侵袭性前列腺癌的倾向的诊断套件，其包括针对goi表达产物特异性的一组寡核苷酸，针对goi表达产物特异性的探针。通常，本发明的诊断套件包含一种或多种试剂，其允许对如在本文中上文所定义的(一个或多个)标记基因或goi的特异性检测。根据本发明，诊断套件的试剂或成分可以被包括在一个或多个容器或单独的实体中。试剂的性质由套件意图针对的检测方法来确定。此外，所述套件可以包括一定量的已知核酸分子，其能够被用于对套件的校准或者作为内部控制。通常，用于检测(一个或多个)标记基因或goi表达产物的诊断套件可以包括辅助成分，如pcr缓冲剂、dntp、聚合酶、离子(如二价阳离子或单价阳离子)、杂交溶液等。这样的成分是本领域技术人员已知的，并且可以根据所执行的检测方法而变化。另外，所述套件可以包括指令页，和/或可以提供关于所获得的结果的相关性的信息。在其他方面中，本发明涉及用于例如在个体中检测、诊断、监测或预测前列腺癌或朝向侵袭性与惰性前列腺癌的进展的方法，其至少包括确定样本中(一个或多个)标记基因或goi水平的步骤。术语“确定(一个或多个)标记基因或goi的水平”指代确定(一个或多个)标记基因或goi表达产物的存在或量。因此，术语“(一个或多个)标记基因或goi的水平”意指(一个或多个)标记基因或goi表达产物(例如，转录物)的存在或量，和/或对(一个或多个)标记基因或goi的存在或量的确定。对(一个或多个)标记基因或goi表达产物的存在或量的确定可以通过本领域已知的任何方式来完成。在本发明的优选实施例中，通过对核酸的测量来完成对(一个或多个)标记基因或goi表达产物的存在或量的确定。因此，(一个或多个)表达水平可以通过涉及对由基因编码的mrna的检测的方法来确定。例如，可以通过纯化从样本获得的核酸分子(例如，rna或cdna)，然后与如在本文中上文所定义的特异性寡核苷酸探针杂交，来估计(一个或多个)标记基因或goi表达的核酸水平的测量。可以通过视觉或借助合适的设备来完成对表达水平的比较。用于检测mrna或表达产物的方法是本领域技术人员已知的。备选地，可以在dna阵列或微阵列方法中检测标记基因或goi表达的核酸水平。通常，来源于待测试患者的样本核酸被处理和标记，优选利用荧光标签。随后，这样的核酸分子可以在利用与本发明的标记基因相对应的固定化捕获探针的杂交方法中使用。用于执行微阵列分析的合适手段是本领域技术人员已知的。在标准设置中，dna阵列或微阵列包括固定化的高密度探针以检测基因的数量。阵列上的探针与标记基因序列的一个或多个部分互补。通常，cdna、pcr产物和寡核苷酸用作探针。基于dna阵列或微阵列的检测方法通常包括以下步骤：(1)从样本中隔离mrna，并且任选地将mrna转化成cdna，并且随后标记该rna或cdna。在针对微阵列技术手册中描述了用于隔离rna、将其转化成cdna并标记核酸的方法。(2)将来自步骤1的核酸与针对标记基因的探针杂交。来自样本的核酸能够利用染料来标记，诸如荧光染料cy3(红色)或cy5(蓝色)。通常，控制样本被利用不同的染料来标记。(3)检测来自样本的核酸与探针的杂交，并且至少定性地并且更具体地定量地确定样本中被调查标记基因的mrna的量。能够基于信号强度的差异来估计在样本与控制之间表达水平的差异。这些能够通过适当的软件来测量和分析，所述软件诸如但不限于例如由affymetrix所提供的软件。与所使用的标记基因相对应的探针的数量没有限制，其被点在dna阵列上。同样地，标记基因能够由两个或更多个探针来表示，所述探针与基因的不同部分杂交。探针是针对每个所选标记基因而设计的。这样的探针通常是包括5-50个核苷酸残基的寡核苷酸。更长的dna能够通过pcr或化学地合成。用于合成这样的寡核苷酸并将其应用在基质上的方法在微阵列领域是周知的。除了标记基因外的基因也可以被点在dna阵列上。例如，可以将表达水平没有显著改变的基因的探针点在dna阵列上以使测定结果标准化，或者比较多个阵列或不同测定的测定结果。备选地，(一个或多个)标记基因或goi表达的核酸水平可以在定量rt-pcr方法中检测，优选在感兴趣的逆转录转录物之后以实时pcr方法来检测。通常，作为第一步，根据本领域技术人员已知的任何合适的方法将转录物逆转录成cdna分子。随后可以基于如上文所描述获得的第一dna链执行定量或实时pcr方法。优选地，可以将作为该类型的基于fret的主要探针的taqman或分子信标探针用于定量pcr检测。在这两种情况下，所述探针用作内部探针，其与位于感兴趣靶区域侧面的一对相对引物结合使用，优选与如在本文中上文所定义的一组(一个或多个)标记基因特异性寡核苷酸结合使用。在扩增目标片段后，所述探针可以在引物位点之间的识别序列处被选择性地结合到产物，由此导致相对于目标频率增加的fret信令的增加。优选地，用于根据本发明的定量pcr方法的taqman探针可以包括约22至30个碱基的如上文所定义的特异性寡核苷酸，所述碱基两端利用fret对进行标记。通常，5'末端将具有较短波长的荧光团，诸如荧光素(例如，fam)；并且3'末端通常利用较长波长的荧光猝灭剂(例如，tamra)或非荧光猝灭剂化合物(例如，黑洞猝灭剂)进行标记。优选地，被用于定量pcr的探针(特别是如在本文中上文所定义的探针)在报告染料附近的5'末端不具有鸟嘌呤(g)，以便避免在探针降级之后报告荧光的淬灭。被用于根据本发明的定量pcr方法的分子信标探针优选使用fret交互来检测和量化pcr产物，每个探针具有5'荧光标记的末端以及3'猝灭剂标记的末端。探针结构的该发夹或茎环配置优选包括具有两个短自我结合末端的茎以及具有约20至30个碱基的长内部目标特异性区域的环。也可以在本发明的上下文中采用的备选检测机制涉及仅利用环结构制造并且不具有短的互补茎区域的探针。也可以被用于本发明的上下文的定量pcr的备选的基于fret的方法基于使用两个杂交探针，所述探针结合到目标上的相邻位点，其中，第一探针在3'末端处具有荧光供体标签，并且第二探针在其5'末端处具有荧光受体标签。在又一实施例中，作为另外的附加步骤，关于癌症的存在或阶段或者癌症的进展的决定可以基于比较步骤的结果。在根据在本文中上文在标记基因或goi的上下文中所提供的对应定义的所述方法中，可以诊断或预测恶性、激素敏感的前列腺癌，或者这可以诊断或预测朝向(侵袭性)前列腺癌的进展，作为针对恶性前列腺癌的标记。在另一实施例中，本发明涉及用于检测、诊断、监测或预测(侵袭性)前列腺癌或朝向(侵袭性)前列腺癌的进展的方法，其至少包括以下步骤：(a)针对goi表达产物的表达水平，对从怀疑患有前列腺癌的至少一个个体获得的至少一个样本中进行测试；(b)针对goi表达产物的表达水平，在至少一个控制样本中进行测试；(c)确定步骤(a)和(b)的表达中的差异；并且(d)基于步骤(c)中获得的结果，决定前列腺癌的存在或阶段或者朝向侵袭性前列腺癌的进展。在一个实施例中，可以在人体或动物体外，例如在从患者或个体获得的样本中，来执行该诊断方法的步骤a)、b)、c)和/或d)。在另一方面中，本发明涉及用于诊断、监测或预测例如侵袭性的前列腺癌或朝向侵袭性前列腺癌的进展的方法，其中，所述方法区分良性和侵袭性前列腺癌，所述方法包括以下步骤：(a)确定(一个或多个)标记基因或goi的水平，(b)确定样本中的参考基因的表达水平；(c)将测量到的(一个或多个)标记基因或goi的表达水平标准化为参考基因的表达；并且(d)将经标准化的表达水平与被选取用于排除良性前列腺癌的预定截止值进行比较，其中，高于所述截止值的标准化表达水平指示侵袭性前列腺癌，其中，所述截留值在-2和+2之间，优选大约为0。表达结果可根据本领域技术人员已知的任何合适的方法来标准化。通常，将使用本领域技术人员已知的这种测试或对应的公式来将表达数据进行标准化，以使得能够区分基因表达水平的实际变化与由于测量过程而导致的变化。对于微阵列，可以将鲁棒多阵列平均值(rma)用作标准化方法。在特定实施例中，通过应用以下公式来生成标准化值：n(cq感兴趣基因)＝mean(cq参考基因)–(cq感兴趣基因)其中，n(cq感兴趣基因)是针对所选的感兴趣基因的标准化基因表达值；其中，mean(cq参考基因)是参考基因的所选组合的pcrcq值的算术平均值；其中，(cq感兴趣基因)是感兴趣基因的pcrcq值。在特定实施例中，通过应用以下公式来生成标准化值：n(cq感兴趣基因)＝mean(cq参考基因)–(cq感兴趣基因)其中，n(cq感兴趣基因)是针对所选感兴趣基因的标准化基因表达值；其中，mean(cq参考基因)是选自tbp、hprt1、actb、rplp0、polr2a、b2m、pum1、k-alpha-1和alas-1中的至少两个参考基因的pcrcq值的算术平均值；其中，(cq感兴趣基因)是感兴趣基因的pcrcq值。在特定实施例中，通过应用以下公式来生成标准值：n(cq感兴趣基因)＝mean(cq参考基因)–(cq感兴趣基因)其中，n(cq感兴趣基因)是针对所选感兴趣基因的标准化基因表达值；其中，mean(cq参考基因)是参考基因tbp、hprt1、actb和rplp0的pcrcq值的算术平均值；其中，(cq感兴趣基因)是感兴趣基因的pcrcq值。在特定实施例中，通过应用以下公式来生成标准化值：n(cq感兴趣基因)＝mean(cq参考基因)–(cq感兴趣基因)其中，n(cq感兴趣基因)是针对所选感兴趣基因的标准化基因表达值；其中，mean(cq参考基因)是参考基因tbp、hprt1、pum1、k-alpha-1和alas-1的pcrcq值的算术平均值，其中，(cq感兴趣基因)是感兴趣基因的pcrcq值。示例性参考基因尤其包括智人tata盒结合蛋白(tbp)、智人次黄嘌呤磷酸核糖转移酶1(hprt1)、智人肌动蛋白，β、mrna(actb)、智人60s酸性核糖体磷蛋白p0mrna(rplp0)、智人山松醇rna结合组成员1(pum1)、聚合酶(rna)ii(dna定向的)多肽a、220kda(polr2a)，β-2-微球蛋白(b2m)、微管蛋白-α-1b(k-alpha-1)、氨基乙酰丙酸-δ-合酶(alas-1)。在优选实施例中，参考基因的组合选自tata盒结合蛋白(tbp)、智人次黄嘌呤磷酸核糖基转移酶1(hprt1)、智人肌动蛋白、β，mrna(actb)、智人60s酸性核糖体磷蛋白p0mrna(rplp0)、智人山松醇rna结合族成员(pum1)、聚合酶(rna)ii(dna导向的)多肽a、220kda(polr2a)、β2-微球蛋白(b2m)、微管蛋白-α-1b(k-alpha-1)、氨基乙酰丙酸-δ-合成酶(alas-1)。在特定实施例中，签名基因的表达水平被标准化为参考基因的表达，其中，参考基因优选为持家基因，并且其中，持家基因优选为tbp、hprt1、actb、rplp0、pum1、polr2a或b2m。在另一优选实施例中，参考基因的组合包括tbp、hprt1一级从包括actb、rplp0、pum1、polr2a、b2m、k-alpha-1(tuba1b)或alas-1的组中选择的至少一个、至少两个或者至少三个额外的参考基因。在另一优选实施例中，参考基因的组合包括tbp、hprt1一级从包括actb、rplp0、pum1、k-alpha-1(tuba1b)或alas-1的组中选择的至少两个额外的参考基因。特别优选的组合是tbp、hprt1、actb、rplp0。另一特别优选的组合是tbp、hprt1、pum1、k-alpha-1、alas-1。在图10中公开了对参考基因的详细描述，所述包括其对应的核苷酸序列的转录物id(ncbirefseq)和seqidno、对应氨基酸序列的蛋白质id(蛋白质加入)和seqidno。此外，图10公开了针对每个参考基因的用于生成针对参考基因特异性的扩增子的正向引物、反向引物以及特异性地结合扩增子的探针序列。如在本文中上文所描述的，可以在核苷酸上确定(一个或多个)标记基因或goi的表达水平。优选的是确定(一个或多个)标记基因或goi转录物的表达水平。另外，可以确定样本中的持家基因的水平。如在本文中所使用的，术语“参考基因”指代任何合适的基因，例如，指代在选择的生物体中稳定表达和可连续检测的基因、基因产物、表达产物、蛋白质或蛋白质变体。所述表达优选可以在相同的样本中执行，即，在相同的样本中确定(一个或多个)标记基因或goi的水平以及参考基因的水平。如果在相同的样本中执行所述测试，则可以执行如在本文中所描述的单个检测或多路复用检测方法。为了执行多路复用检测，可以修改引物和/或探针寡核苷酸的浓度。此外，可以修改如缓冲剂、离子等的其他成分的浓度和存在，与制造商的指示相比被上调或下调或下降。此外，表达结果可以与来自参考案例或数据库的已知结果进行比较。所述比较可以额外地包括标准化过程，以便提高结果的统计相关性。可以根据本领域技术人员已知的任何合适的方法对表达结果进行标准化，例如，根据如标准分数、学生t测试、学生化残差测试、标准化时刻文本或系数变异测试等的标准化统计学方法。通常，将使用本领域技术人员已知的这种测试或对应的公式来将表达数据标准化，以使得能够在基因表达水平的实际变化与由于测量过程而导致的变化进行区分。基于在步骤(a)和(b)中获得的表达结果和/或在步骤(c)中获得的标准化结果，可以执行与针对goi表达水平的截止值的比较。(一个或多个)标记基因或goi的表达水平在所述截止值之上表示侵袭性前列腺癌，由此排除良性前列腺癌形式或健康情况或健康组织形式，所述截止值在约-3和+3之间、-3和+2.75之间、-3和+2.5之间、-3和+2.25之间、-3和+2之间、-3和+1.75之间、-3和+1.5之间、-3和+1.25之间、-3和+1之间、-3和+0.75之间、-3和+0.5之间、-3和+0.25之间、-3和0之间、-2.75和+3之间、-2.5和+3之间、-2.25和+3之间、-2和+3之间、-1.75和+3之间、-1.5和+3之间、-1.25和+3之间、-1和+3之间、-0.75和+3之间、-0.5和+3之间、-0.25和+3之间、或者0和+3之间。更优选的是截止值大约为0，例如，0.9、0.8、0.7、0.6、0.5、0.4、0.3、0.2、0.1或者-0.9、-0.8、-0.7、-0.6、-0.5、-0.4、-0.3、-0.2或-0.1。如果测量的和/或标准化的表达水平低于所指示的截止值，则这可以被看作是指示个体对于前列腺癌是健康的，或者仅患有良性前列腺癌，而不是侵袭性前列腺癌。在另一方面中，本发明涉及一种数据采集方法，至少包括以下步骤：(a)针对(一个或多个)标记基因或goi的表达在个体中进行测试；并且(b)将在步骤(a)中确定出的表达与控制水平进行比较。可以根据如在本文中上文所定义的步骤执行针对(一个或多个)标记基因或goi的表达的测试。优选地，可以将测试作为对(一个或多个)标记基因或goi的核酸的测量来执行。所述测试可以在个体中执行，即，在体内执行；或者在个体外部执行，即，离体或体外地执行。在数据采集的方法的上下文中所使用的术语“控制水平”指代如在本文中上文所定义的在本文中所提及的标记基因的表达或者在正常控制或癌性控制中的其他合适标记的表达。所述控制水平的状态、性质、数量和状况可以根据需要进行调整。优选地，可以使用正常、健康的控制水平。表达与控制水平的比较可以根据估计、计算、评估或处理数据的任何合适的方法来执行，并且特别旨在检测两个数据集之间的差异。可以进一步执行对差异的显著性的统计学评估。合适的统计学方法是本领域技术人员已知的。所获得的数据和信息可以通过本领域技术人员已知的合适的信息学或计算机方法或工具来存储、积累或处理，和/或以适当的方式来呈现，以允许从业者将数据用于一个或多个后续推论或结论步骤。另外，可以确定样本中如在本文中上文所定义的参考基因的水平。备选地，可以利用任何其他合适的试剂来执行对参考基因的确定，或者所述确定可以与如在本文中所述的对核酸的存在或量的检测相组合地执行。在另外的方面中，本发明涉及识别适合于前列腺癌治疗的个体的方法，包括：(a)在从个体获得的样本中针对(一个或多个)标记基因或goi表达进行测试；(b)针对参考基因的表达在所述样本中进行测试和/或针对(一个或多个)标记基因或goi的表达在控制样本中进行测试；(c)将步骤(a)的表达的水平相对于步骤(b)的水平进行分类，并计算各自的pcpi；(d)将所述个体识别为适合于接收前列腺癌疗法，其中，所述个体的样本被分类为具有上调或下调水平的(一个或多个)标记基因或goi表达水平或者指示侵袭性疾病的pcpi。如在本文中所使用的，术语“相对于步骤(b)的水平对步骤(a)的表达水平进行分类”意指将在测试样本中针对goi的表达与在控制样本中针对goi的表达进行比较，例如，在相对于适合的标准化参考进行标准化之后和/或在计算相应的pcpi之后。根据对pcpi的计算，当基因表达水平与控制样本相比显著不同时，可认为个体适合于前列腺癌治疗。如在本文中所使用的术语“将个体或个体的群组分级为前列腺癌疗法”意指个体被识别为属于一组相似的个体，其最佳疗法形式是前列腺癌疗法，例如，根据如在本文中上文所描述的对pcpi的计算的结果的疗法。被认为适合于进行前列腺癌治疗或者被分级至如在本文中上文所描述的前列腺癌疗法的个体可以接收针对本领域技术人员已知的这种前列腺癌形式的任何合适的治疗性处置。具体地，如在本文中所使用的术语“前列腺癌疗法”指代本领域技术人员已知的任何适合的前列腺癌疗法，并且优选包括通过移除作为雄性性激素产物的主要器官的睾丸的手术去势，通过例如抑制雄性激素的生成或者通过禁止雄性激素受体活动的化学去势，细胞毒素，化学疗法，放射疗法(外部束放射疗法、近距离放射疗法)，冷冻疗法，局部疗法如hifu消融(高频超声消融)，或热消融或者其组合，优选激素疗法和放射疗法的组合。通常，被认为适合于进行前列腺癌治疗的个体可能被认为患有(侵袭性)前列腺癌，或者在将来易患这种疾病，例如在接下来的1至24个月内。对应地识别的或分级的个体可以利用抑制性药物复合物治疗。在另外的实施例中，对应地识别的个体可以利用抑制性药物复合物与额外的癌症疗法相组合来处置。术语“额外的癌症疗法”指代本领域技术人员已知的任何类型的癌症疗法。优选的是已知用于前列腺癌的癌症疗法形式。例如，该术语包括所有适合形式的化学疗法、放射疗法、手术、抗体疗法等。备选地，对应地识别的或分级的个体也可以仅利用一种或多种癌症疗法进行治疗，诸如化学疗法、放射疗法、手术、抗体疗法等。优选的是通常用于前列腺癌的癌症疗法，更优选的是被用于侵袭性前列腺癌的癌症疗法。在本发明的另外实施例中，如在本文中上文所描述的针对适用性或者针对分级的分类方法也可以被用于监测对个体的处置，例如，被分类为患有侵袭性前列腺癌的个体。所述监测过程可以在延长的时间段期间作为表达确定来执行，例如，在处置会话期间或之后，在1、2、3、4、5、6、7、8、9、10周，1、2、3、4、5、6、7、8、9、10个月，或者1、2、3年或更长期间。可以以适当的间隔来执行确定步骤，例如，每周、2周、3周、每个月、2个月、3个月、6个月、12个月等。在本发明的另外的实施例中，可以调整在本文中上文所提到的任何治疗方案，例如根据监测过程的结果以任何适当的方式强制或减弱或改变。在本发明的另外的实施例中，基于如在本文中上文所描述的(一个或多个)标记基因或goi的表达以及对应的pcpi来识别适合于进行侵袭性前列腺癌治疗个体的方法还可以基于一种或多种不同生物标记的表达而与一种或多种类似识别方法相组合。优选的是确定血液中前列腺特异性抗原(psa)的水平。因此，如果血液中的psa水平遇到约2至5或更多ng/ml的范围，优选约2.2至4.8ng/ml或更多的范围，2.4至4.4ng/ml或更多的范围，1.6至4.2ng/ml或更多的范围，或者2.8-4.0ng/ml或更多的范围，更优选约2.5-4ng/ml或更多的范围，则个体可被认为患有恶性前列腺癌，或者可能在不久的将来发展为恶性前列腺癌，即，在接下来的1、2、3、4、5、6、12、14、48个月之内。针对(一个或多个)标记基因或goi表达的测试以及对pcpi的确定可以根据如在本文中上文所定义的步骤来执行。在本发明的优选实施例中，如上文所提及的诊断、检测、监测或预测是在从个体获得的样本上执行的。如在本文中所使用的术语“从个体获得的样本”涉及经由本领域技术人员已知的适合的方法从个体获得的任何生物材料。在本发明的上下文中使用的样本应当优选以临床上可接受的方式收集，更优选以保留核酸(特别是rna)或蛋白质的方式收集。生物学样本可以包括身体组织和流体，例如血液、汗液和尿液。此外，生物学样本可以包含来源于上皮细胞或包括上皮细胞的细胞群体的细胞提取物，优选是癌性上皮细胞或来源于疑似为癌性的组织的上皮细胞。甚至更优选地，生物学样本可以包含来源于腺体组织的细胞群体，例如，样本可能来源于男性个体的前列腺。另外，如果需要，细胞可以从所获得的身体组织和流体中纯化，并且然后被用作生物学样本。可以池化样本，尤其是在初始处理之后。然而，也可以使用非池化的样本。在本发明的特定实施例中，生物学样本的内容也可以被提交至富集步骤。例如，样本可以与针对特定细胞类型的细胞膜或细胞器(例如，前列腺细胞)特异性的配体相接触，例如利用磁性颗粒进行功能化。随后，可以将由磁性颗粒浓缩的材料用于如在本文中上文或下文所描述的检测和分析的步骤。在本发明的特定实施例中，可以获得和/或使用活组织检查或移除样本。这样的样本可以包括细胞或细胞裂解物。此外，可以经由流体或液体样本(例如，血液、尿液等)的过滤过程来富集细胞(例如，肿瘤细胞)。这样的过滤过程也可以与基于如在本文中上文所描述的配体特异性交互的富集步骤相组合。在本发明的特别优选的实施例中，样本可以是组织样本、活组织检查样本、尿液样本、尿液沉淀物样本、血液样本、唾液样本、精液样本、包括循环肿瘤细胞的样本、或者包含前列腺分泌的外泌体的样本。血液样本例如可以是血清样本或血浆样本。在对前列腺癌的处置中，能够使用对癌细胞具有活性抵抗的化合物或药物复合物。所述药物复合物可以包括激素抑制剂，优选抗雄性激素或雄性激素拮抗剂，如螺内酯、醋酸环丙孕酮、氟他胺、尼鲁米特、比卡鲁胺、酮康唑、非那雄胺或度他雄胺。在另外的特定实施例中，本发明设想了一种监测前列腺癌发展的方法，其涵盖确定(一个或多个)标记基因或goi，优选与如在本文中上文所描述的确定参考基因相结合，在特定时间段内，即，在重复的确定步骤之后，例如，每4周、6周、两个月、4个月、6个月、8个月、12个月、1.5年、2年、2.5年、3年、4年或任何其他合适的时间段等。所述方法可以提供以下数据，所述数据示出了(一个或多个)标记基因或goi的水平相较于控制(例如，非癌性控制、癌性控制或者从相同个体获得的早期数据)的增加或降低。借助于本领域技术人员已知的适合的统计学方法，可以确定所述曲线内的位置。根据所述曲线内的位置，即，在所述曲线的增大部分或下降部分中，可以诊断存在或将来发展的前列腺癌。相应地，设想到了使用药物复合物。优选地，任何这样的确定可以与次级生物标记的确定相结合，例如，针对前列腺癌的标记，特别是psa。在低psa水平(达2.0-4.0ng/ml)的情况下，可以相对于早期前列腺癌，即良性或激素依赖性/激素敏感的前列腺癌来分析goi数据。在较高psa水平(高于约20ng/ml，例如约30、40或50ng/ml)的情况下，可以相对于更晚期的前列腺癌(例如，激素抵抗的前列腺癌)来分析所述数据。如在本文中所使用的“激素敏感的阶段i至iv前列腺癌”表示能够根据国际抗癌联盟(uicc)的tnm分类分为阶段i至iv的前列腺癌。如在本文中所使用的“激素敏感的复发性前列腺癌”表示其生长和进展被调节并依赖于男性性激素的前列腺癌。这种男性性激素的优选范例是雄性激素。如在本文中所使用的“激素敏感的转移性前列腺癌”表示其生长和进展被调节并依赖于男性性激素的前列腺癌。这种男性性激素的优选范例是雄性激素。如在本文中所使用的“激素不敏感前列腺癌”表示其生长和进展不被调节并且独立于男性性激素的前列腺癌。这种男性性激素的优选范例是雄性激素。本发明的另一方面涉及一种计算机程序产品，其包括被存储在计算机可读介质上或者能从通信网络下载的计算机可读代码，所述计算机可读代码在计算机上运行时实施在本文中上文所描述的任何一种方法的一个或多个步骤或所有步骤。可以利用一个或多个计算机可读介质的任何组合。所述计算机可读介质可以是计算机可读信号介质或计算机可读存储介质。计算机可读存储介质例如可以是但不限于电子的、磁的、光学的、电磁的、红外的或半导体的系统、装置或设备，或者前述的任何合适的组合。计算机可读存储介质的更具体的范例(非穷举列表)包括以下项：具有一条或多条线的电连接、便携式计算机磁盘、硬盘、随机存取存储器(ram)、只读存储器(rom)、可擦除可编程只读存储器(eprom或闪存)、光纤、、便携式压缩盘只读存储器(cd-rom)、光学存储设备、磁存储设备、或者前述任何适当的组合。在本文档的上下文中，计算机可读存储介质可以是任何有形介质，其能够包含或存储由指令执行系统、装置或设备使用或者与其结合使用的程序。计算机可读信号介质可以包括在其中体现计算机可读程序代码的传播的数据信号，例如，在基带中或者作为载波的一部分。这样的传播的信号可以采取多种形式中的任意形式，其包括但不限于：电磁、光学或者其任何适当的组合。计算机可读信号介质可以是计算机可读存储介质之外的任何计算机可读介质，并且其能够通信、传播或传输供指令执行系统、装置或设备使用或与其结合使用的程序。体现在计算机可读介质上的程序代码可以使用任何适当的介质来传输，所述介质包括但不限于：无线、有线、光缆、rf等，或者前述的任何适当的组合。用于执行针对本发明的各方面的操作的计算机程序代码可以以一种或多种编程语言的任何组合来编写，所述语言包括：面向对象编程语言，诸如java、smalltalk、c++等；以及常规程序编程语言，例如“c”编程语言或类似的编程语言。程序代码可以完全在用户的计算机上、部分在用户的计算机上作为独立的软件包、部分在用户的计算机上以及部分在远程计算机上、或者全部在远程计算机或服务器上执行。在后一种场景中，所述远程计算机可以通过任何类型的网络(包括局域网(lan)或广域网(wan))被连接到用户的计算机，或者可以被连接到外部计算机(例如，通过使用互联网服务提供商的互联网)。这些计算机程序指令还可以被存储在计算机可读介质中，其能够指导计算机、其他可编程数据处理装置或其他设备以特定方式运行，使得被存储在计算机可读介质中的指令产生包括实施在本文中所指定的功能/动作的指令的制品。所述计算机程序指令也可以被加载到计算机、其他可编程数据处理装置或其他设备上，以使得在计算机、其他可编程装置或其他设备上执行一系列操作步骤来产生计算机实施的过程，使得在计算机或其他可编程装置上执行的指令提供用于实施在本文中所指定的功能/动作的过程。除非另外地定义，否则在本文中所使用的所有技术和科学术语具有与本发明所属领域的普通技术人员通常理解的相同的含义。下面的范例和附图是为了例示说明的目的而提供的。因此，应当理解，范例和附图不应当被解释为限制性的。本领域技术人员将能够清楚地设想到对在此阐述的原理的进一步修改。范例范例1-用于构建前列腺癌预后指数(pcpi)的基因选择为了选择基因候选以构建pcpi，如在wo2010131194和wo2010131195中所描述的，针对推定的预后基因标记pde4d7的相关性研究了各种分子路径，如在http://csbi.ltdk.helsinki.fi/anduril/tcga-gbm/table4_2.html中所概述的。示出了显著相关性的那些分子路径被选择用于下游分析(图1)。此外，从以下文献中选择与转移性和/或激素难治性前列腺癌相关的基因候选：-gorlovip等人，candidatepathwaysandgenesforprostatecancer:ameta-analysisofgeneexpressiondata；bmcmedicalgenomics2009，2:48-stanbroughm等人：increasedexpressionofgenesconvertingadrenalandrogenstotestosteroneinandrogen-independentprostatecancer；cancerres2006；66:2815-2825-tamurak等人，molecularfeaturesofhormone-refractoryprostatecancercellsbygenome-widegeneexpressionprofiles；cancerres2007；67(11):5117-25-lapointej等人，geneexpressionprofilingidentifiesclinicallyrelevantsubtypesofprostatecancer；pnas2003；101(3):8110816-suny等人，optimizingmolecularsignaturesforpredictingprostatecancerrecurrence。prostate，69:1119-1127(2009)总共选择了(参见图1)被报道可能与前列腺癌进展有关的967个基因以供将来的分析。为了构建19-基因预后签名，即，一组感兴趣标记基因，使用以下数据集：1taylorbs等人，integrativegenomicprofilingofhumanprostatecancer。cancercell18，11-22，2010(geo数据集id:gse21032)-boormansjl等人，identificationoftdrd1asadirecttargetgeneoferginprimaryprostatecancer。intjcancer2013年7月15日；133(2):335-45(geo数据集id:gse41408)-suny等人，optimizingmolecularsignaturesforpredictingprostatecancerrecurrence。theprostate，69:1119-1127(2009)(geo数据集id：gse25136)-sbonera等人，molecularsamplingofprostatecancer:adilemmaforpredictingdiseaseprogression。bmcmedicalgenomics2010，3:8(geo数据集id：gse16560)-nagakawa等人，atissuebiomarkerpanelpredictingsystemicprogressionafterpsarecurrencepost-definitiveprostatecancertherapy。plosone3(5)，e2318(2010)(geo数据集id：gse10645)为了进一步测试和验证所构建的前列腺癌预后指数(pcpi)，使用以下数据集：erhon等人，discoveryandvalidationofaprostatecancergenomicclassifierthatpredictsearlymetastasisfollowingradicalprostatectomy。plosone8(6)，e66855(2013)(geo数据集id：gse46691)对gse基因表达数据的处理各自的cel文件从geo(基因表达综合数据库)下载：http://www.ncbi.nlm.nih.gov/geo/。cel文件数据被上传到表达控制台(affymetrixinc；build1.3.1.187)中，并且在适当的情况下使用由affymetrixinc.提供的适当的探针组注释文件(即，在affymetrixinc平台上运行的数据集：gse21032、gse41408、gse25136)进行预处理。针对在dasl平台上运行的数据集(即，gse16560、gse10645)，使用如由geo提供的数据序列矩阵文件进行下游数据分析。参考基因被怀疑具有独立于被处理的样本的稳定表达，并且因此能够被用作内部标准以对pcr分析的输出cq值进行标准化，从而使结果可比较地独立于所使用的输入样本的量。尽管这样的基因被认为是稳定的，但是在其表达中始终存在一些变异，并且该稳定性也能够取决于被分析的组织。出于这样的原因，建议在对pcrcq值的标准化中使用多于一个的参考基因，并且使用在被分析的特定类型的组织/样本中呈现低变异性的一组基因(c.l.andersen，jljensen和tf“normalizationofreal-timequantitativereversetranscription-pcrdata:amodel-basedvarianceestimationapproachtoidentifygenessuitedfornormalization,appliedtobladderandcoloncancerdatasets”，cancerres.，第64卷，第15期，第5245-5250页，2004年8月；j.vandesompele，k.depreter，f.pattyn，b.poppe，n.vanroy，a.depaepe和f.speleman，“accuratenormalizationofreal-timequantitativert-pcrdatabygeometricaveragingofmultipleinternalcontrolgenes”，genomebiol.，第3卷，第7期，p.research0034，2002年6月)。执行在本研究中所使用的9个参考基因的初始选择。通过在所有经分析的临床样本上运行biogazellesoftware工具(qbase+withgenormanalysisj.hellemans,g.mortier,a.d.paepe,f.speleman,andj.vandesompele,“qbaserelativequantificationframeworkandsoftwareformanagementandautomatedanalysisofreal-timequantitativepcrdata,”genomebiol.，第8卷，第2期，p.r19，2007年2月)，进行对用于标准化的参考基因组的最终选择。pcr测定的输出cq值本质上是对数的(底数为2)，并且与样本中存在的mrna的量成反比。我们使用下面的公式来标准化原始的cq值：n(cq感兴趣基因)＝mean(cq参考基因)–(cq感兴趣基因)其中，n(cq感兴趣基因)是针对所选感兴趣基因的标准化基因表达值；其中，mean(cq参考基因)是所选参考基因组合的pcrcq值的算术平均值；其中，(cq感兴趣基因)是感兴趣基因的pcrcq值。在使用除qrt-pcr之外的其他技术来测量参考基因或感兴趣基因的表达的情况下，pcrcq值将被相应技术的标准化测量结果来替代(例如，针对dna微阵列的rma(鲁棒多阵列平均值)标准化基因表达值，或者针对rna测序的fpkm(每映射的百万片段的外显子的每千碱基的片段)标准化基因表达值)。前列腺癌进展指数(pcpi)的计算与在初级处置之后具有或没有进展的患者组之间上调相比，选定的感兴趣基因(goi)被分组为在初级处置之后具有或没有进展的患者组之间被下调。从每个分析的患者样本的标准化基因表达数据计算针对下调基因的平均基因表达值(gev_av_goi_down)以及针对上调基因的平均基因表达值(gev_av_goi_up)。每个患者样本的前列腺癌进展指数pcpi被确定为：pcpi＝(gev_av_goi_up)-(gev_av_goi_down)所计算的pcpi被用于任何进一步的统计学数据分析。pcpi_17计算(基于定量实时pcr数据)使用以下公式计算pcpi：pcpi＝mean(n(cqpcpi基因上调))–mean(n(cqpcpi基因下调))其中，mean(n(cqpcpi基因上调))是针对以下基因的标准化基因表达值(参见上文)的算术平均值：bgn、birc5、col1a1、col3a1、col5a2、dyrk2、inhba、thbs2和vcan并且其中，mean(n(cqpcpi基因下调))是针对以下基因的标准化基因表达值(参见上文)的算术平均值：azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4和srd5a2。pcpi_18计算(基于定量实时pcr数据)使用以下公式来计算pcpi：pcpi＝mean(n(cqpcpi基因上调))–mean(n(cqpcpi基因下调))其中，mean(n(cqpcpi基因上调))是针对以下基因的标准化基因表达值(参见上文)的算术平均值：bgn、birc5、col1a1、col3a1、col5a2、dyrk2、inhba、thbs2和vcan并且其中，mean(n(cqpcpi基因下调))是针对以下基因的标准化基因表达值(参见上文)的算术平均值：pde4d、azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4和srd5a2pcpi_19计算(基于定量实时pcr数据)使用以下公式来计算pcpi：pcpi＝mean(n(cqpcpi基因上调))–mean(n(cqpcpi基因下调))其中，mean(n(cqpcpi基因上调))是针对以下基因的标准化基因表达值(参见上文)的算术平均值：bgn、birc5、col1a1、col3a1、col5a2、dyrk2、inhba、thbs2和vcan并且其中，mean(n(cqpcpi基因下调))是针对以下基因的标准化基因表达值(参见上文)的算术平均值：pde4d5、pde4d7、azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4和srd5a2。前列腺癌进展指数(pcpi)与临床参数对患者结果的相关性分析利用xlstat版本2014.1.03执行对pcpi的所有统计学分析(例如，逻辑回归分析、roc分析、cox回归分析等)以及其和患者结果的相关性与临床参数(如psa、pgleason、pt阶段)的比较。结果针对以上基因表达数据集中的不同表达，在初级处置之后没有显示其疾病的进展的前列腺癌患者与那些显示了下列临床终点中任一个的疾病进展的患者组之间，研究了967个选定基因候选，所述临床终点为：生化复发、通过检测局部或远处转移的临床复发、前列腺癌特异性死亡。表2(参见图2)提供了57个选定基因的概述，所述基因被发现显著(p<0.05)差异地表达，并且五个测试数据集中的至少三个中的上文所提到的患者组之间在相同方向上(即，上调或下调)的患者组之间进行调节。随后，根据以下标准将基因分为三类：rank_3：在最大3个数据集中观测到的在相同方向上以显著的p值(p<0.05)差异地表达的所有基因，或者具有非独特注释的基因rank_2：在4个或5个数据集中观测到的在相同方向上以显著的p值(p<0.05)差异地表达的所有基因rank_1：在4或5个数据集中观测到的在相同方向上以显著p值(p<0.05)差异地表达的所有基因，但限于上调的9个基因和下调的10个基因。优选的pcpi签名包括以下19个基因或者由其组成：pde4d5、pde4d7、azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2、col1a1、col3a1、col5a2、inhba、thbs2、vcan、bgn、birc5和dyrk2。由于并非所有数据集都提供关于pde4d异构体(即，pde4d5和pde4d7)的转录水平的信息，所以经证实的结果基于pde4d基因的测量结果，因为在数据集gse21032和gse41408中pde4d的表达与pde4d7的表达非常相关(标准化为pde4d5的表达)；因此，所确定的pcpi_18包括以下18个基因：pde4d、azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2、col1a1、col3a1、inhba、thbs2、vcan、bgn、birc5、dyrk2。针对其中未测量pde4d基因的这样的数据集(即，gse16560、gse10645)，所确定的pcpi_17包括以下17个基因：azgp1、fbln1、ilk、krt15、meis2、mybpc1、page4、srd5a2、col1a1、col3a1、inhba、thbs2、vcan、bgn、birc5、dyrk2。前列腺癌患者在初级处置之后pcpi与临床结果数据的相关性表3(参见图3)示出了关于pcpi_18或pcpi_17的性能的概述，以针对数据集gse21032、gse41408、gse25136、gse16560、gse10645来预测在初级处置(通常是前列腺疗法)之后10-15年内远处转移的发展的初级终点。针对在数据集gse16560中研究的患者，在turp(经尿道移除术)期间检测到前列腺癌，并且随后保守地管理患者(即，不移除前列腺)。针对在数据集gse10645中研究的患者，针对终点对患者的监测仅在生化复发之后开始。这些数据集被用于构建pcpi签名(训练数据)。示出了每组患者的数量(无进展与进展至转移)以及来源于roc分析的auc(曲线下面积)。auc指示不同数据集中pcpi的相对功率以预测群组内的初级终点。表4(参见图4)示出了pcpi_18的性能，以针对数据集gse46691来预测在初级处置之后10-15年内远处转移的发展的初级终点；该数据集不被用于训练pcpi，而是被用作独立的验证数据集(验证数据)。针对在数据集gse10645中研究的患者，针对终点对患者的监测仅在生化复发之后开始。示出了每组患者的数量(无进展与进展至转移)以及来源于roc分析的auc(曲线下面积)。auc指示不同数据集中pcpi的相对功率，以预测群组内的初级终点。表5(参见图5)示出了pcpi_18或pcpi_17的性能，以针对数据集gse21032、gse41408、gse16560、gse10645，与标准临床参数(如治疗前psa，活组织检查或病理学gleason分数，或临床/病理学疾病阶段)相比，在多变量cox回归分析中预测在初级处置(通常是前列腺疗法)之后10-15年内发生远处转移的初级终点。针对每个个体数据集示出了卡方以及pcpi的危险比和个体临床参数。表6(参见图6)示出了pcpi_18的性能的概况，以针对数据集gse21032、gse41408、gse25136预测在初级处置(通常是前列腺疗法)后10-15年内生化疾病复发(bcr)发展的初级终点。示出了每组患者的数量(没有进展与进展至bcr)以及来源于roc分析的auc(曲线下面积)。auc指示不同数据集中pcpi的相对功率以预测群组内的初级终点。表7(参见图7)示出了pcpi_18的性能，以针对数据集gse21032、gse41408、gse25136，与标准临床参数(如治疗前psa，活组织检查或病理学gleason分数，或临床/病理学疾病阶段)相比，在多变量cox回归分析中预测在初级处置(通常是前列腺疗法)之后10-15年内发生生化疾病复发(bcr)的发展的初级终点。针对每个个体数据集示出了卡方以及pcpi的危险比和个体临床参数。表8(参见图8)示出了pcpi_18的roc曲线截止分析，以支持针对主动监管(as)或主动治疗(例如，前列腺移除术、放射疗法、激素疗法)的患者分级的临床决策。表中所示的截止值选自roc曲线，从而具有侵袭性疾病的>90％男性被正确分类(对应于90％的敏感性)。该截止值允许将具有非常低风险谱的134的分级到例如主动监管而不是例如手术。该群组中无进展生存到超过约10年随访的转移性疾病的终点接近85％。将相同的方法应用于临床模型(病理学gleason分数)，结果是gleason分数<＝6的截止将导致仅有57名男性分级到例如主动监管而不是例如手术。在该患者群组中的无进展生存将接近90％，但代价是许多具有非进展疾病的男性将被分级至例如手术；与病理学gleason分数相比，使用pcpi_18分级的人数是as的两倍多，而风险谱非常相似(分别为85％和90％无进展生存)。通过pcpi_18和病理学gleason的组合模型可以进一步增加分级的能力。使用该模型，146名男性(相比于134名)将被分级至as，在超过10年内无进展生存概率约为87％。针对所显示的患者群组的截止分析是针对总群组(545名患者)、病理学gleason分数>＝7的子群组(482名患者)、以及病理学gleason分数>＝8的另一子群组(211名患者)来执行的。图11、12和13涉及根据研究获得的分析，该分析对约500位患者执行纵向随访，与pcpi_19(图11)的性能相比，来源于rnaseq数据的gpsu得分分析12种癌症相关基因和5种参考基因的表达，并且按照该方法进行计算，所述方法能够从dejanknezevic等人的文章“analyticalvalidationoftheoncotypedxprostatecancerassay-aclinicalrt-pcrassayoptimizedforprostateneedlebiopsies”，bmcgenomics(2013)，14:690(图12)中推断出，并且ccp分数来源于31个基因的表达水平，并且被计算，其能够从jackcuzick等人的文章“prognosticvalueofanrnaexpressionsignaturederivedfromcellcycleproliferationgenesforrecurrenceanddeathefromprostatecancer:aretrospectivestudyintwocohorts”，lancetoncol.(2011)；12(3):245-255(图13)推断出。为了更好地比较，gpsu和ccp得分已经被缩放到1到5之间的范围。图11、12和13示出了根据不同的患者组的5年或10年的不同复发风险(参见以下描述)。在x轴上，通过nccn风险组定义了患者组；vl&lr＝非常低和低风险；fir＝有利的中间风险；uir＝不利的中间风险；hr＝高风险。nccn是美国常用的肿瘤学指南(https://www.nccn.org/professionals/physician_gls/f_guidelines.asp)。在y轴上，通过4类不同分数对患者组进行定义：1-2；2-3；3-4和4-5。在4x4网格中，根据其nccn临床风险特性并且根据其针对pcpi、gpsu或ccp的分数，针对网络的任何细胞来选择患者。根据临床风险组(最下面一行)或者根据分数类别(表格右侧栏)来计算不同的风险。为了清楚起见，在细胞内仅描绘了5年的bcr复发风险。风险描述是：5年bcr-5年以上生化复发10年cr-10年以上临床复发转移10年pcsm-10年以上前列腺癌特异性死亡率10年om-10年以上总体死亡率(由于所有原因)图11、12和13中下划线的数字表示与其他签名相比改善性能的pcpi的区域。与积极治疗的临床决策相比，属于这些类别的患者是积极监管的潜在患者，因此应当具有尽可能小的复发风险。pcpi在这些领域胜过其他签名。序列表<110>皇家飞利浦有限公司<120>前列腺癌预后的方法<130>p141442014pf00611<160>204<170>patentinversion3.5<210>1<211>7979<212>dna<213>homosapiens<400>1cagcagcaggctcagacctgcttccctggacatttccgggaccgtgagcgagggaaccac60gttgccctggattcttgccagctgtacaaagttgaccaggaaaatggctcagcagacaag120cccggacactttaacagtacctgaagtggataatccgcattgtccaaacccgtggctgaa180cgaagaccttgtgaaatccttgcgagaaaacctgttgcagcatgagaagtccaagacagc240gaggaaatcggtttctcccaagctctctccagtgatctctccgagaaattcccccaggct300tctgcgcagaatgcttctcagcagcaacatccccaaacagcggcgtttcacggtggcaca360tacatgttttgatgtggacaatggcacatctgcgggacggagtcccttggatcccatgac420cagcccaggatccgggctaattctccaagcaaattttgtccacagtcaacgacgggagtc480cttcctgtatcgatccgacagcgattatgacctctctccaaagtctatgtcccggaactc540ctccattgccagtgatatacacggagatgacttgattgtgactccatttgctcaggtctt600ggccagtctgcgaactgtacgaaacaactttgctgcattaactaatttgcaagatcgagc660acctagcaaaagatcacccatgtgcaaccaaccatccatcaacaaagccaccataacaga720ggaggcctaccagaaactggccagcgagaccctggaggagctggactggtgtctggacca780gctagagaccctacagaccaggcactccgtcagtgagatggcctccaacaagtttaaaag840gatgcttaatcgggagctcacccatctctctgaaatgagtcggtctggaaatcaagtgtc900agagtttatatcaaacacattcttagataagcaacatgaagtggaaattccttctccaac960tcagaaggaaaaggagaaaaagaaaagaccaatgtctcagatcagtggagtcaagaaatt1020gatgcacagctctagtctgactaattcaagtatcccaaggtttggagttaaaactgaaca1080agaagatgtccttgccaaggaactagaagatgtgaacaaatggggtcttcatgttttcag1140aatagcagagttgtctggtaaccggcccttgactgttatcatgcacaccatttttcagga1200acgggatttattaaaaacatttaaaattccagtagatactttaattacatatcttatgac1260tctcgaagaccattaccatgctgatgtggcctatcacaacaatatccatgctgcagatgt1320tgtccagtctactcatgtgctattatctacacctgctttggaggctgtgtttacagattt1380ggagattcttgcagcaatttttgccagtgcaatacatgatgtagatcatcctggtgtgtc1440caatcaatttctgatcaatacaaactctgaacttgccttgatgtacaatgattcctcagt1500cttagagaaccatcatttggctgtgggctttaaattgcttcaggaagaaaactgtgacat1560tttccagaatttgaccaaaaaacaaagacaatctttaaggaaaatggtcattgacatcgt1620acttgcaacagatatgtcaaaacacatgaatctactggctgatttgaagactatggttga1680aactaagaaagtgacaagctctggagttcttcttcttgataattattccgataggattca1740ggttcttcagaatatggtgcactgtgcagatctgagcaacccaacaaagcctctccagct1800gtaccgccagtggacggaccggataatggaggagttcttccgccaaggagaccgagagag1860ggaacgtggcatggagataagccccatgtgtgacaagcacaatgcttccgtggaaaaatc1920acaggtgggcttcatagactatattgttcatcccctctgggagacatgggcagacctcgt1980ccaccctgacgcccaggatattttggacactttggaggacaatcgtgaatggtaccagag2040cacaatccctcagagcccctctcctgcacctgatgacccagaggagggccggcagggtca2100aactgagaaattccagtttgaactaactttagaggaagatggtgagtcagacacggaaaa2160ggacagtggcagtcaagtggaagaagacactagctgcagtgactccaagactctttgtac2220tcaagactcagagtctactgaaattccccttgatgaacaggttgaagaggaggcagtagg2280ggaagaagaggaaagccagcctgaagcctgtgtcatagatgatcgttctcctgacacgta2340acagtgcaaaaactttcatgccttttttttttttaagtagaaaaattgtttccaaagtgc2400atgtcacatgccacaaccacggtcacacctcactgtc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