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: 8598789
• 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/8598789
• 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：PPA的总体假设是确定某些遗传标记的风险评估，如miRNAs、单核苷酸错配修复基因或SNPs，以及X连锁基因(如TSPX)，因为有证据表明它们与前列腺癌有关。 第一个项目是研究可能作为前列腺癌标志物的miRNAs，这些miRNAs通过抑制癌基因或肿瘤抑制基因的表达而发挥作用。这些研究旨在描绘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SNPs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，TSPX是一种肿瘤抑制基因，也是AR功能的辅助抑制基因，因为它参与了前列腺癌的风险和进展。PPA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：优势：研究前列腺癌的三种分子生物标记物在大量前列腺癌标本(处于不同的病理阶段)中的表达是朝着建立关于患者疾病发展潜力的识别系统迈出的重要一步。这些知识在设计治疗方法方面可能有很大价值。这项研究还将有助于目前缺失的前列腺癌病理生物学方面的知识。对这三类生物标志物功能的分子机制的研究也得到了很好的考虑，并将促进与这些生物标志物功能有关的基础知识的发展。特别值得注意的一点是，沿着所提出的路线对分子生物标记物的研究以前没有进行过，这使得这是一项非常新颖的努力。拟议研究的成功可能会带来