A Serum Marker for Aggressive Prostate Cancer

侵袭性前列腺癌的血清标志物

• 批准号: 7101297
• 负责人: Donna M Peehl
• 金额: $ 43.13万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-28 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7101297
• 关键词: neoplasm /cancer; prostate neoplasms; proteins; serum

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.

描述(申请人提供)：PSA时代结束了。在美国，广泛的血清PSA(前列腺特异性抗原)筛查和广泛的活检导致了越来越小的前列腺癌的检测，因此血清PSA不再与癌症相关。在今天被诊断为前列腺癌的患者中，血清PSA只与前列腺重量相关[即良性前列腺增生(BPH)]。血清PSA与前列腺癌关系的丧失凸显了寻找前列腺癌新标记物的紧迫性。然而，任何新的标记物都必须与前列腺癌的数量成比例，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，这些癌症中的许多都不会危及生命。我们以前的工作表明，Gleason分级4/5模式在癌症中的百分比(%)是目前已知的最强的预后标志物。根治性前列腺癌根治术时，4/5级(最大)癌症指数每增加10%，就有10%的生化失败率，这是通过可检测到的和不断上升的血清PSA来衡量的。因此，我们认为迫切需要一个与Gleason 4/5级癌的数量和/或百分比成比例的血清标记物。我们将通过两种综合和综合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。我们的具体目标是：1)检测前列腺癌患者手术前后血清中侵袭性癌的候选蛋白标记物；2)通过对BPH和4/5级癌组织的蛋白质组学分析，寻找其他候选血清标记物。有助于实现我们目标的资源包括存档的、固定的、连续切片的和地图绘制的根治性前列腺切除标本、一个特征良好的冰冻前列腺组织库、一个非常大的血清库、全面的临床和组织病理学数据库、最先进的技术和熟练的人员。