EPS Markers in the Early Detection of Prostate Cancer

EPS 标记物在前列腺癌早期检测中的应用

• 批准号: 6879182
• 负责人: STEVEN Sidney SMITH
• 金额: $ 27.09万
• 依托单位: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6879182
• 关键词: DNA methylation; age difference; biomarker; biopsy; cancer risk; clinical research; diagnosis design /evaluation; early diagnosis; enzyme activity; enzyme mechanism; genetic mapping; glutathione transferase; human subject; male; neoplasm /cancer diagnosis; neoplasm /cancer genetics; neoplastic growth; neoplastic transformation; patient oriented research; polymerase chain reaction; prostate neoplasms; prostate specific antigen; secretion; telomerase

DESCRIPTION (provided by applicant): Prostate cancer (PCA) is the most commonly diagnosed cancer in American males and the second leading cause of cancer deaths. Current screening modalities lack the sensitivity and specificity necessary for the optimal detection of organ confined and potentially curable disease. It is well established that the hallmarks of oncogenic transformation include general chromosome instability, widespread aberrations in cytosine methylation patterning and upregulation of the telomerase system. This has led to recent reports which have identified telomerase and DNA methylation status as candidate markers for the early detection of prostate cancer. Our experiments suggest that there may also be a direct link between ectopic telomerase expression and aberrations in methylation patterning. Taken together, these findings provide the basis for the use of these markers in the detection of tumor and tumor progression. Our long term goal is to exploit expressed prostatic secretion (EPS) as a non-invasive specimen in the diagnosis of prostate cancer. To this end, we propose to validate a model of prostate cancer diagnosis based on the synchronous use of multiple markers of risk classification. Based on our preliminary findings with a series of 28 patients, we expect that age, prostate specific antigen levels (PSA), digital rectal exam (DRE), and EPS markers of telomerase over-expression and local methylation change will provide a highly reliable test for the detection of prostate cancer. Our hypothesis is that methylation status at the pi-class glutathione-S transferase gene GSTP1 in DNA obtained from EPS specimens will be a reliable predictor of the presence of PCA when coupled with telomerase component levels determined on these same EPS specimens and augmented with patient age, PSA levels and DRE information. We hypothesize that this combination will have higher assay sensitivity, specificity, positive and negative predictive values than any single assay alone, including PSA. Using methodology that has now been benchmarked in EPS specimens and a cohesive team of clinicians and scientists, EPS will be collected and analyzed from 300 patients, who, as part of a local or multi-institutional trial, undergo TRUSP (transrectal ultrasound of the prostate) and biopsy.

描述（由申请人提供）：前列腺癌（PCA）是美国男性最常见的癌症，也是癌症死亡的第二大原因。当前的筛查方式缺乏最佳检测受限制和可能治愈疾病的器官所必需的敏感性和特异性。众所周知，致癌的标志包括一般染色体不稳定性，胞质甲基化模式的广泛畸变和端粒酶系统的上调。这导致了最近的报道，这些报道确定了端粒酶和DNA甲基化状态是早期发现前列腺癌的候选标记。我们的实验表明，异位端粒酶表达与甲基化模式的像差之间也可能存在直接联系。综上所述，这些发现为在检测肿瘤和肿瘤进展的检测中使用这些标记提供了基础。我们的长期目标是将表达的前列腺分泌（EPS）作为诊断前列腺癌的非侵入性标本。为此，我们建议根据多种风险分类标记的同步使用前列腺癌诊断模型。根据我们对一系列28例患者的初步发现，我们期望年龄，前列腺特异性抗原水平（PSA），数字直肠检查（DRE）和端粒酶过表达的EPS标记和局部甲基化变化，将为检测前列腺癌的检测提供高度可靠的测试。我们的假设是，从EPS标本获得的DNA中PI级谷胱甘肽-S转移酶基因GSTP1处的甲基化状态将是PCA存在的可靠预测指标，当与端粒酶成分与在这些相同的EPS样品上确定的端粒酶成分水平相结合，并与患者年龄，PSA水平和PSA水平和DRE信息相同。我们假设这种组合将比仅包括PSA在内的任何单个测定法具有更高的测定敏感性，特异性，正和阴性预测值。使用现已在EPS标本和临床医生和科学家组成的凝聚力团队中进行基准测试的方法，将从300名患者中收集和分析EPS，作为当地或多机构试验的一部分，他们接受TRUSP（前列腺的跨直直型超声）和Bibopsy。