A Serum Marker for Aggressive Prostate Cancer

描述（由申请人提供）：PSA时代已经结束。在美国，广泛的血清PSA（前列腺特异性抗原）筛查和广泛的活组织检查已经导致检测到更小的前列腺癌，使得血清PSA不再与癌症相关。在当今诊断为前列腺癌的患者中，血清PSA仅与前列腺重量相关[即，良性前列腺增生（BPH）]。血清PSA与前列腺癌的任何关系的丧失强调了寻找前列腺癌新标记物的紧迫性。然而，任何新的标志物都必须与前列腺中的癌症数量成比例，因为尸检研究表明前列腺癌无处不在，到70岁时，大约80%的男性患有前列腺癌。试图检测所有这些癌症是不可取的，因为前列腺癌的死亡率相对较低，这告诉我们许多癌症并不危及生命。我们以前的工作表明，癌症中Gleason 4/5级模式的百分比（%）是目前已知的最强的预后标志物。在根治性直肠癌切除术时，指数（最大）癌症的4/5级每增加10%，通过可检测和升高的血清PSA测量的生化失败率为10%。因此，我们提出，迫切需要与Gleason 4/5级癌症的量和/或%成比例的血清标志物。我们将通过两种综合全面的方法来实现我们的目标，即确定侵袭性前列腺癌的血清标志物。我们的具体目的是1）测量前列腺切除术前和后患者血清中侵袭性癌症的候选蛋白标志物，和2）通过BPH和4/5级癌症组织的蛋白质组学分析鉴定另外的候选血清标志物。资源，将有助于实现我们的目标，包括档案，固定，连续切片和映射根治性前列腺切除术标本，一个银行的良好特点冷冻前列腺组织，一个非常大的血清库，全面的临床和组织病理学数据库，国家的最先进的技术，和熟练的人员。

DESCRIPTION (provided by applicant): The PSA era is over. In the U.S., widespread serum PSA (prostate-specific antigen) screening and extensive biopsies have led to the detection of ever smaller prostate cancers, such that serum PSA no longer has a correlation with cancer. In today's patients diagnosed with prostate cancer, serum PSA correlates only with prostate weight [i.e., benign prostatic hyperplasia (BPH)]. The loss of any relationship of serum PSA to prostate cancer emphasizes the urgency of finding a new marker for prostate cancer. Any new marker, however, must be proportional to the amount of cancer in the prostate because autopsy studies have shown that prostate cancer is ubiquitous, and by the age of 70, approximately 80% of men have prostate cancer. It is not advisable to attempt to detect all of these cancers, because the relatively small death rate from prostate cancer tells us that many of these cancers are not life threatening. Our previous work has shown that the percentage (%) of Gleason grade 4/5 pattern in the cancer is the strongest prognostic marker currently known. For every 10% increase in grade 4/5 in the index (largest) cancer at the time of radical prostatectomy, there is a 10% biochemical failure rate as measured by a detectable and rising serum PSA. Therefore, we propose that a serum marker proportional to the amount and/or % of Gleason grade 4/5 cancer is critically needed. We will pursue our goal of identifying a serum marker of aggressive prostate cancer through two integrated and comprehensive approaches. Our specific aims are to 1) measure candidate protein markers of aggressive cancer in sera from patients pre- and post- prostatectomy and 2) identify additional candidate serum markers by proteomic analysis of BPH and grade 4/5 cancer tissues. Resources that will contribute towards achieving our goal include archival, fixed, serially sectioned and mapped radical prostatectomy specimens, a bank of well-characterized frozen prostatic tissues, a very large serum bank, comprehensive clinical and histopathologic databases, state-of-the-art technology, and skilled personnel.