MOLECULAR MARKERS FOR PROSTATE CANCER DETECTION

前列腺癌是#年癌症发病率和死亡率的主要原因。 美国。1998年，它将占39,000人的死亡人数 新增确诊病例18.9万例。当前的筛查方法 包括结合PSA使用直肠指诊 对血液进行检测，以确定有风险的个人。这种方法论 充其量仍未得到证实，并导致侵入性核心活检 已知的假阴性率的大多数个体， 这可能会阻止一些患者参与筛查 努力。我们建议启动对两个已知的分子标记的研究 在检测前列腺癌细胞方面比它们的 正常上皮对应物，端粒酶的表达，以及 高甲基化谷胱甘肽转移酶PI-1启动子的存在 区域DNA。我们已经建立了相当敏感的方法来 并已证明它们在发现LNCaP方面是有效的 在正常射精液中加入肿瘤细胞，但不能提供高比率 假阳性的可能性。此外，我们还发现，稀有基因的表达 HOXC4-6、C8和C10基因的信使RNA转录本 前列腺癌细胞与正常细胞的特征比较 对口单位。我们建议进一步评估这种基因在 从精液和细针中获取前列腺上皮细胞 新诊断患者的抽吸作为一种新的诊断方法 前列腺癌可能导致侵袭性更小和/或更多 提供诊断信息的方法。

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.