A Biomarker Risk Prediction Model for Prostate Cancer

前列腺癌的生物标志物风险预测模型

• 批准号: 10063436
• 负责人: Tamaro Syton Hudson
• 金额: --
• 依托单位: U.S. DEPT/VETS AFFAIRS MEDICAL CENTER
• 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 2020-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10063436
• 关键词: Address; Affect; African American; Annexins; Archives; Benign Prostatic Hypertrophy; Biological; Biological Markers; Biopsy; Biopsy Specimen; Cancer Center; Cancer Patient; Cancer Prognosis; Candidate Disease Gene; Caucasians; Cells; Chaperonin 60; Chemoprevention; Classification; Clinic; Clinical; Communities; Detection; Diagnosis; Diet and Nutrition; Disease; District of Columbia; Early Diagnosis; Ethnic group; Exhibits; Future; Gene Chips; Gene Expression; Gene Expression Profiling; Gene Proteins; Genes; Gleason Grade for Prostate Cancer; Goals; Heat shock proteins; Heat-Shock Proteins 70; Human; Immunohistochemistry; In Situ Hybridization; Individual; Indolent; Logistic Models; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Medical center; Methodology; Microarray Analysis; Modeling; Newly Diagnosed; Normal tissue morphology; Outcome; Pathologist; Pathology; Prostate; Prostate carcinoma; Prostate-Specific Antigen; Proteins; Public Health; RNA; Race; Records; Research; Risk; Sampling; Screening procedure; Serine Proteinase Inhibitors; Source; Specimen; Stains; Statistical Data Interpretation; Statistical Models; Stratification; Subgroup; Testing; Tissue Sample; Tissues; Transrectal Ultrasound; Treatment Efficacy; Tumor Antigens; United States Department of Veterans Affairs; Universities; University Hospitals; Variant; Washington; Western World; advanced prostate cancer; cancer health disparity; cancer prevention; clinical application; cohort; diagnostic screening; differential expression; disease diagnosis; early screening; genetic profiling; genetic signature; health disparity; high risk population; insight; interest; men; molecular marker; mortality; novel therapeutics; overexpression; potential biomarker; predictive marker; predictive modeling; prognostic; prostate biopsy; prostate cancer model; prostate cancer risk; protein expression; risk prediction model; screening; specific biomarkers; trend; tumor registry; urologic

DESCRIPTION (provided by applicant): Modified Project Summary/Abstract Section African American (AA) men are at a greater risk of developing aggressive prostate cancer (PrCa) than are Caucasian men. Therefore, identifying biomarkers involved in aggressive PrCa that can be used to identify AA men for specific and/or novel therapies would provide a major advance in public health. Consequently, there is intense effort to identify potential biomarkers that could independently predict poor clinical outcome and identify novel therapies for men with aggressive PrCa. Notably, heat shock proteins, PrCa Antigen 3, and Serine Protease Inhibitor Kazal-type 1, are all overexpressed in men with PrCa, where as Annexin II is suppressed. Despite the biological importance of these biomarkers, no studies have yet evaluated the significance of these biomarkers in AA men with aggressive PrCa. We believe that Howard's University Hospital urologic clinic which evaluates approximately 200 PrCa patients per year, is an ideal source for studying the importance of biomarkers as predictors of aggressive PrCa in AA men. We propose to evaluate the bi-directional expression of protein and gene signature pairs different in archival tissue samples from AA men who had been diagnosed with an aggressive form of PrCa at the Washington VA Medical Center and Howard and Johns Hopkins University Cancer Centers. The main hypothesis is that the bi-directional expression of genes and proteins is predictive of aggressive, lethal PrCa risk. To test this hypothesis we propose two aims. The first aim will test the hypothesis that microarray gene expression profiling produces bi-directional biomarker signature pairs that can be used to build a risk prediction model for PrCa. The second aim will test the hypothesis that the risk prediction of poor clinical outcome with bi-directional gene and protein expression pairs is superior to the use of a single gene or protein. Candidate pairs include those discovered in Aim 1. We anticipate that these studies may provide insight into selected genes and proteins as reliable predictive biomarkers for identifying aggressive PrCa in AA men, and could inform future human clinical applications for treatment of aggressive PrCa.

描述（由申请人提供）： 非裔美国人（AA）男性比白人男性患侵袭性前列腺癌（PrCa）的风险更大。因此，鉴定参与侵袭性PrCa的生物标志物，可用于鉴定AA男性的特异性和/或新型治疗，将为公共卫生提供重大进展。因此，有大量的努力，以确定潜在的生物标志物，可以独立地预测不良的临床结果，并确定新的治疗男性与积极的PrCa。值得注意的是，热休克蛋白，PrCa抗原3和丝氨酸蛋白酶抑制剂Kazal-1型，都在PrCa男性中过表达，其中膜联蛋白II被抑制。尽管这些生物标志物的生物学重要性，但尚未有研究评估这些生物标志物在患有侵袭性PrCa的AA男性中的意义。我们认为，霍华德大学医院泌尿科诊所每年评估约200例PrCa患者，是研究生物标志物作为AA男性侵袭性PrCa预测因子的重要性的理想来源。我们建议评估双向表达的蛋白质和基因签名对不同的档案组织样本AA男子已被诊断为侵略性形式的PrCa在华盛顿VA医学中心和霍华德和约翰霍普金斯大学癌症中心。主要的假设是基因和蛋白质的双向表达是侵略性的预测， 致命PrCa风险。为了验证这一假设，我们提出了两个目标。第一个目标将测试微阵列基因表达谱产生双向生物标志物签名对的假设，该双向生物标志物签名对可用于构建PrCa的风险预测模型。第二个目标将检验以下假设：用双向基因和蛋白质表达对预测不良临床结果的风险上级使用单个基因或蛋白质。候选对包括在目标1中发现的那些。我们预计，这些研究可能会提供深入了解选定的基因和蛋白质作为可靠的预测生物标志物，用于识别AA男性的侵袭性PrCa，并可能为未来的人类临床应用提供信息，用于治疗侵袭性PrCa。

项目成果

Differential expression of Annexin 2, SPINK1, and Hsp60 predict progression of prostate cancer through bifurcated WHO Gleason score categories in African American men.

膜联蛋白2，Spink1和Hsp60的差异表达通过非裔美国人男性的格里森评分类别来预测前列腺癌的进展。

• DOI: 10.1002/pros.23537
• 发表时间: 2018-08
• 期刊: The Prostate
• 作者: Beyene DA;Naab TJ;Kanarek NF;Apprey V;Esnakula A;Khan FA;Blackman MR;Brown CA;Hudson TS
• 通讯作者: Hudson TS