Role of genetic biomarkers in clinical assessment of prostate cancer

遗传生物标志物在前列腺癌临床评估中的作用

• 批准号: 8764702
• 负责人: RAJVIR DAHIYA
• 金额: --
• 依托单位: VETERANS AFFAIRS MED CTR SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-10-01 至 2016-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8764702
• 关键词: Area; Award; Biological Markers; Biomedical Research; Cancer Patient; Cells; Clinical; Clinical assessments; Color; Core Facility; Data Analyses; Disease Progression; Equipment; Fostering; Funding; Gene Expression; Genes; Genetic; Genetic Markers; Genome; Genomics; Goals; Growth; Health; Healthcare; Human; Image; Individual; Intervention; Investigation; Ions; Knowledge; Life; Link; Literature; Malignant Neoplasms; Malignant neoplasm of prostate; Medical center; MicroRNAs; Microarray Analysis; Mismatch Repair; Mission; Molecular; Morphology; Neoplasm Metastasis; Nucleotides; Oncogenic; Outcome; Pathology; Patient Identification Systems; Patients; Predisposition; Process; Prostate; Prostatic Neoplasms; Publishing; Research; Research Personnel; Research Priority; Resolution; Resources; Risk Assessment; Risk Factors; Role; San Francisco; Scanning; Services; Single Nucleotide Polymorphism; Solid; Specimen; Staging; Staining method; Stains; Sum; Techniques; Technology; Tissues; Tumor Suppressor Genes; Veterans; base; cancer risk; clinically relevant; clinically significant; density; gene repair; in vitro Model; instrumentation; laser capture microdissection; loss of function; next generation; novel; operation; programs; success; tissue culture; tool; tumor; tumor progression

Description: The overall hypothesis of this PPA is to identify risk assessment of certain genetic markers such as miRNAs, single nucleotide mismatch repair genes or SNPs, and X-linked genes (such as TSPX) since there is evidence that they are associated with prostate cancer. The first project is to investigate the miRNAs that may serve as markers of prostate cancer by virtue of their action in suppression of oncogenic or tumor suppressor gene expression. The studies aim at delineating the underlying mechanisms that control these processes. The second project is to investigate the role of SNPs in mismatched repair (MMR) genes in prostate cancer susceptibility and progression. The third project is to investigate involvement in prostate cancer risk of the X-linked tumor suppressor gene (TSPX) which is a tumor repressor and corepressor for AR functions for its involvement in prostate cancer risk and progression. The three projects in the PPA will be supported by three Cores: 1) Administrative Core; 2) Tissue/Morphology/Molecular Core; and 3) Statistical Core. Significance: Strengths: The study of the expression of three types of molecular biomarkers of prostate cancer in a large number prostate specimens (at different stages of pathology) represents an important step towards developing a system of patient identification with respect to their potential for disease progression. This knowledge could be of much value in devising therapy approaches. This research will also contribute to the aspect of knowledge on prostate cancer pathobiology that is currently missing. Studies on the molecular mechanisms of the functions of the three types of biomarkers are also well considered and will advance the fundamental knowledge pertaining to the function of these biomarkers. A particularly noteworthy point is that investigation of molecular biomarkers along the proposed lines has not been undertaken previously making this a highly novel endeavor. The success in the proposed studies could lea

描述：该 PPA 的总体假设是确定某些遗传标记的风险评估，例如 miRNA、单核苷酸错配修复基因或 SNP 以及 X 连锁基因（例如 TSPX），因为有证据表明它们与前列腺癌相关。 第一个项目是研究可作为前列腺癌标志物的 miRNA，因为它们具有抑制致癌或肿瘤抑制基因表达的作用。这些研究旨在描述控制这些过程的潜在机制。第二个项目是研究错配修复 (MMR) 基因中的 S​​NP 在前列腺癌易感性和进展中的作用。第三个项目是研究 X 连锁肿瘤抑制基因 (TSPX) 与前列腺癌风险的关系，该基因是 AR 功能的肿瘤抑制因子和辅抑制因子，与前列腺癌风险和进展有关。 PPA 中的三个项目将得到三个核心的支持： 1) 行政核心； 2）组织/形态/分子核心； 3) 统计核心。 意义： 优点：对大量前列腺标本（处于不同病理阶段）中三种类型的前列腺癌分子生物标志物表达的研究代表了朝着开发患者疾病进展潜力识别系统迈出的重要一步。这些知识对于设计治疗方法可能非常有价值。这项研究还将有助于补充目前缺乏的前列腺癌病理学知识。对三类生物标志物功能的分子机制的研究也得到了充分考虑，并将推进有关这些生物标志物功能的基础知识。特别值得注意的一点是，之前尚未按照所提出的路线对分子生物标志物进行研究，这使得这是一项高度新颖的尝试。拟议研究的成功可能会导致