Methylated Galectin-3 DNA as a Marker for Early Diagnosis of Prostate Cancer

甲基化 Galectin-3 DNA 作为前列腺癌早期诊断的标志物

• 批准号: 7753079
• 负责人: HAFIZ AHMED
• 金额: $ 7.5万
• 依托单位: UNIVERSITY OF MD BIOTECHNOLOGY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7753079
• 关键词: Accounting; Alleles; American Joint Committee on Cancer; Benign Prostatic Hypertrophy; Biological; Biological Assay; Biological Markers; Biopsy; Cancer Etiology; Cessation of life; CpG Islands; Cytosine; DNA; Detection; Development; Diagnosis; Diagnostic; Diagnostic Neoplasm Staging; Digital Rectal Examination; Disease; Early Diagnosis; Figs - dietary; Galectin 3; Gene Expression; Genes; Glutathione S-Transferase; Goals; Hypermethylation; Inflammation; Lead; Liquid substance; Malignant Neoplasms; Malignant neoplasm of prostate; Methods; Methylation; Monitoring for Recurrence; Newly Diagnosed; Oncogenes; Patients; Pattern; Principal Investigator; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Family; RARB gene; Research Project Grants; Sampling; Screening for Prostate Cancer; Screening for cancer; Screening procedure; Sensitivity and Specificity; Serum; Serum Markers; Site; Specificity; Specimen; Staging; Telomerase; Test Result; Testing; Therapeutic; Tissues; Tumor Suppressor Genes; Tumor Tissue; Tumor stage; United States; Urine; Ursidae Family; base; bisulfite; cancer diagnosis; cohort; design; effective therapy; galactose-binding protein; improved; member; men; programs; promoter; successful intervention; tool; tool development; tumor; tumor progression

DESCRIPTION (provided by applicant): Prostate cancer is the second most common cancer in men, and the second leading cause of cancer death. However, patients with prostate cancer can be effectively treated and cured, when diagnosed in early stages (i.e. the stages when cancer is still confined to the prostate gland). 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 tissue and urine specimens. Results from these studies 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.

描述（由申请人提供）： 前列腺癌是男性第二大常见的癌症，也是癌症死亡的第二大原因。然而，在早期诊断出癌症时，可以有效治疗和治愈前列腺癌的患者（即，癌症仍局限于前列腺的阶段）。结合数字直肠检查，前列腺特异性抗原（PSA）测试已被广泛用于在早期阶段检测前列腺癌。 PSA水平升高可能是前列腺癌的指示。但是，诸如前列腺增大或炎症之类的各种疾病会导致PSA水平升高。相反，尽管存在前列腺癌，PSA水平可能正常。因此，由于高度普遍的假阳性和负PSA测试结果，用于早期检测前列腺癌的PSA筛查方法不适合。因此，迫切需要一个可靠的预测前列腺癌的标记。据信，由于基因启动子的高甲基化而导致肿瘤抑制基因表达的转录沉默被认为有助于肿瘤进展。因此，甲基化的DNA可以用作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等级和阶段呈正相关，因此这些甲基化DNA的检测不一定适合在早期阶段鉴定前列腺癌，尤其是在I和II阶段（有效治疗和治愈的关键阶段）。与肿瘤组织的正常阶段和更高的阶段相比，最近发现，前列腺癌基因（PCG）在I和II肿瘤阶段被严重甲基化。 PCG中的甲基化允许开发基于PCR的敏感和特定的工具，这些工具清楚地鉴定了组织中前列腺癌的早期阶段以及血清和尿液等生物液中的早期阶段。拟议的研究的目的是使用大量的组织和尿液标本来建立“概念证明”。这些研究的结果将导致开发一种非侵入性诊断工具，不仅是为了早期检测，而且还用于治疗指导和复发性监测前列腺癌的尿液中。