MOLECULAR MARKERS FOR PROSTATE CANCER DETECTION

用于前列腺癌检测的分子标记

• 批准号: 2828530
• 负责人: L MICHAEL GLODE
• 金额: $ 11.33万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2828530
• 关键词: DNA methylation; clinical research; cytodiagnosis; diagnosis design /evaluation; fine needle aspiration; flow cytometry; genetic markers; genetic promoter element; glutathione transferase; homeobox genes; human subject; immunomagnetic separation; male; messenger RNA; natural gene amplification; neoplasm /cancer diagnosis; neoplastic cell; prostate neoplasms; semen; telomerase

Prostate cancer is a leading cause of cancer morbidity and mortality in the United States. In 1998, it will account for 39,000 deaths with 189,000 new cases being diagnosed. Current screening methodology involves use of digital rectal examination in combination with PSA testing of the blood to identify individuals at risk. This methodology remains unproved at best, and leads to invasive core biopsy in the majority of individuals which is known to have a false negative rate, and which may deter some patients from participating in screening efforts. We propose to initiate studies of two molecular markers known to be of value in detecting prostate cancer cells compared to their normal epithelial counterparts, the expression of telomerase, and the presence of hypermethylated Glutathione Sulfotransferase Pi-1 promoter region DNA. We have established reasonably sensitive methodologies for detection and have shown that they are efficacious in finding LNCaP tumor cells added to normal ejaculates, while not providing a high rate of false positivity. Moreover, we have found that the expression of rare messenger RNA transcripts for the HOXC4-6, C8, and C10 genes characterize prostate cancer cells compared to their normal counterparts. We propose to further evaluate such gene expression in prostate epithelial cells obtained from ejaculates and fine needle aspirates of newly diagnosed patients as a novel diagnostic approach to prostate cancer which could lead to less invasive and/or more informative methods of diagnosis.

前列腺癌是癌症发病率和死亡率的主要原因， 美国的 1998年，它将造成39，000人死亡， 新增确诊病例18.9万例。 目前的筛选方法 涉及直肠指检与PSA联合使用 通过血液检测来识别有风险的人。 这种方法 最好的情况下仍然未经证实，并导致在 大多数已知具有假阴性率的个体， 这可能会阻止一些患者参加筛查 努力 我们建议对两种已知的分子标记进行研究， 与它们相比，在检测前列腺癌细胞方面具有价值。 正常上皮对应物，端粒酶表达，以及 存在高甲基化谷氨酸硫转移酶Pi-1启动子 区域DNA。 我们已经建立了合理敏感的方法， 检测，并已表明他们是有效的，在寻找LNCaP 肿瘤细胞添加到正常的射精，而不是提供一个高利率 假阳性。此外，我们还发现， HOXC 4 -6、C8和C10基因的信使RNA转录物 与正常细胞相比，表征前列腺癌细胞 同行 我们建议进一步评估这样的基因表达， 从精液和细针中获得的前列腺上皮细胞 作为一种新的诊断方法， 前列腺癌，这可能会导致更少的侵入性和/或更多的 诊断的信息方法。