Early detection of prostate cancer in urine

描述（由申请人提供）：前列腺癌是男性第二大常见癌症，也是癌症死亡的第二大原因。然而，当前列腺癌在早期阶段被诊断出来时，它可以有效地治疗和治愈。结合直肠指检，前列腺特异性抗原（PSA）检测已被广泛应用于早期前列腺癌的检测。PSA水平升高可能是前列腺癌的征兆。然而，各种情况，如前列腺肿大或炎症可导致PSA水平升高。相反，即使有前列腺癌，PSA水平也可能是正常的。因此，由于PSA检测结果假阳性和阴性非常普遍，因此PSA筛查方法不适合早期发现前列腺癌。因此，迫切需要一种可靠的前列腺癌早期检测标志物。由于基因启动子的高甲基化，肿瘤抑制基因表达的转录沉默被认为有助于肿瘤的进展。因此，甲基化dna可以作为早期检测癌症的生物标志物。但是，大多数基因的甲基化与肿瘤的分级和分期呈正相关，因此检测这些甲基化dna并不一定适用于早期前列腺癌的识别，特别是在I期和II期（有效治疗和治愈的关键阶段）。最近发现，与正常和晚期肿瘤组织相比，前列腺癌基因（PCG）在I期和II期肿瘤中被严重甲基化。PCG中的甲基化使得基于pcr的敏感和特异性工具得以开发，这些工具可以清楚地识别组织以及血清和尿液等生物液体中的前列腺癌的早期阶段。拟议研究的目标是利用大量尿液标本建立“概念证明”。这些研究结果与PSA检测结果相结合，将有助于开发一种非侵入性的诊断工具，不仅可以早期发现前列腺癌，还可以用于尿中前列腺癌的治疗指导和复发监测。

DESCRIPTION (provided by applicant): Prostate cancer is the second most common cancer in men, and the second leading cause of cancer death. However, when prostate cancer is diagnosed in its early stages, it can be effectively treated and cured. Combined with the digital rectal examination, the prostate specific antigen (PSA) test has been widely used to detect prostate cancer in its early stages. An elevated PSA level may be an indication of prostate cancer. However, various conditions such as enlargement or inflammation of prostate can cause elevated levels of PSA. Conversely, PSA levels may be normal despite the presence of prostate cancer. Thus, the PSA screening method for early detection of prostate cancer is not suitable due to highly prevalent false positive and negative PSA test results. Therefore, a reliable marker for early detection of prostate cancer is urgently needed. Transcriptional silencing of tumor suppressor gene expression due to hypermethylation of the gene promoters is believed to contribute to the neoplastic progression. Thus, methylated DNAs can serve as biomarkers for early detection of cancer. But, the methylation of most genes correlates positively with tumor grade and stage and thus the detection of these methylated DNAs is not necessarily suitable to identify prostate cancer at early stages, especially at stages I and II (the critical stages for effective treatment and cure). A prostate cancer gene (PCG) has recently been found to be heavily methylated in stages I and II tumor compared to the normal and later stages of tumor tissues. The methylation in the PCG allows development of PCR-based sensitive and specific tools that clearly identify the early stages of prostate cancer in tissues as well as in biological fluids such as serum and urine. The goal of the proposed studies is to establish 'proof of concept' using a large number of urine specimens. Results from these studies in combination with PSA test result will lead to the development of a non-invasive diagnostic tool not only for early detection, but also for therapeutic guidance and recurrence monitoring of prostate cancer in urine. PUBLIC HEALTH RELEVANCE Patients with prostate cancer can be effectively treated and cured, when diagnosed in early stages (i.e. the stages when the cancer is still confined to the prostate gland). The objective of this project is to develop a non-invasive, sensitive and specific method that clearly identifies the early stages of prostate cancer in urine.