Immunoseroproteomics in Prostate Cancer: Focus on Health Disparities

前列腺癌的免疫血清蛋白质组学：关注健康差异

• 批准号: 8485667
• 负责人: Carlos A. Casiano
• 金额: $ 8.25万
• 依托单位: LOMA LINDA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8485667
• 关键词: Address; African American; Antibodies; Antibody Formation; Autoantibodies; Biological Markers; Biopsy; Blood Tests; Build-it; Cancer Detection; Cancer Patient; Caucasians; Caucasoid Race; Clinical; Detection; Diagnosis; Diagnostic; Disease Progression; Enhancing Antibodies; Enzyme-Linked Immunosorbent Assay; Evidence based intervention; Goals; Inflammation; Instruction; Knowledge; Malignant Neoplasms; Malignant neoplasm of prostate; Mass Spectrum Analysis; Messenger RNA; MicroRNAs; Monitor; Obesity; Oxidative Stress; Patients; Pilot Projects; Plasma; Population; Prevention; Prostate-Specific Antigen; Proteins; Proteomics; Research; Screening for Prostate Cancer; Sensitivity and Specificity; Serodiagnoses; Serological; Serum; Specificity; Spottings; Stress; Techniques; Testing; Therapeutic; Therapeutic Intervention; Time; Tissue Microarray; Translating; Tumor Antigens; Tumor Tissue; Tumor-Derived; Two-Dimensional Polyacrylamide Gel Electrophoresis; Universities; Western Blotting; cancer diagnosis; case control; cohort; comparative; design; digital; ethnic difference; health disparity; high risk; improved; men; mortality; novel; novel strategies; prostate cancer cell; protein profiling; rectal; response; screening; sensor; survivin; transcriptional coactivator p75; tumor

Improving eariy prostate cancer (PCa) detection in African-American (AA) men is fundamental for reducing racial disparities in PCa mortality. PCa detection and management relies mainly on PSA screening. While the use of this test has improved the eariy diagnosis and management of PCa, its limitations in regards to specificity, particularly among obese AA men, demands complementary non-invasive approaches for enhancing early PCa detection, monitoring disease progression, and evaluating therapeutic responses. The implementation of these novel approaches will depend on the identification of more specific and sensitive biomarkers that could be tailored to AA men. We will use an immunoseroproteomics approach focused on profiling serum autoantibodies to tumor-associated antigens (TAAs) and serum exosomes in AA and Caucasian (CC) PCa patients. The project fills the gap of the lack of systematic immunoseroproteomics studies for biomarker identification in AA patients with PCa. It builds on our key observations indicating that: 1) PCa sera contain autoantibodies to TAAs involved in tumor stress survival such as LEDGF/p75 and Survivin, and could act as sensors of inflammation and an augmented state of cellular oxidative stress (ASCOS); 2) TAA mini-arrays enhance antibody detection in PCa patients and distinguish between cancer and normal populations; 3) customized mini-arrays of PCa-specific TAAs are most effective in enhancing immunoserological diagnosis of PCa; 4) PCa patient sera have exosomes that contain stress survival proteins such Survivin and PRDX3; and 5) there might be ethnic differences in the protein profiles or levels of serum exosomes. Our central hypothesis is that proteomic profiling of serum anti-TAA antibodies and exosomes in AA and CC PCa patients will yield novel biomarkers for enhancing early PCa detection and management, leading to the implementation of evidence-based interventions tailored to AA men. The aims are to: 1) profile anfi-TAA antibodies in sera from AA and CC PCa patients using immunoproteomics and customized TAA mini-arrays; 2) profile tumor-derived exosomal proteins in sera from AA and CC PCa patients by proteomics approaches; and 3) To determine in a comparative case-controlled pilot study if young AA men with no PCa diagnosis have increased serum levels of anti-TAA autoantibodies and tumorderived exosomal proteins, compared to AA men with PCa. Our goal is to identify and validate novel serum biomarkers that could be tailored to AA men to enhance the serological diagnosis of PCa, monitor disease progression, and guide personalized therapies.

改善非洲裔美国人（AA）男性的Eariy前列腺癌（PCA）检测是减少的基础 PCA死亡率的种族差异。 PCA检测和管理主要依赖于PSA筛选。尽管 该测试的使用改善了PCA的耳鸣诊断和管理，其限制在 特异性，特别是在肥胖的AA男子中，需要互补的非侵入性方法 增强早期PCA检测，监测疾病进展和评估治疗反应。这 这些新颖方法的实施将取决于更具体和更敏感的识别 可以针对AA男子量身定制的生物标志物。我们将使用关注的免疫蛋白质组学方法 在AA和 高加索（CC）PCA患者。该项目填补了缺乏系统的免疫蛋白质组学的空白 AA PCA患者的生物标志物鉴定研究。它基于我们的主要观察结果，表明： 1）PCA血清包含与参与肿瘤应力存活的TAA的自身抗体，例如LEDGF/P75和 Survivin，可以充当炎症的传感器和细胞氧化应激的增强状态 （ascos）; 2）TAA迷你阵列增强了PCA患者的抗体检测并区分癌症 和正常人口； 3）PCA特异性TAA的定制迷你阵列最有效地增强 PCA的免疫体诊断； 4）PCA患者血清的外泌体包含应力存活 蛋白质此类rovivin和prdx3; 5）蛋白质曲线或水平可能存在种族差异 血清外泌体。我们的中心假设是血清抗TAA抗体的蛋白质组学分析和 AA和CC PCA患者中的外泌体将产生新型的生物标志物，以增强早期PCA检测和 管理层，导致实施针对AA男子量身定制的基于证据的干预措施。目的 为：1）使用免疫蛋白质组学和 定制的TAA迷你阵列； 2）从AA和CC PCA中介绍了血清中肿瘤衍生的外泌体蛋白 蛋白质组学方法的患者； 3）在比较病例对照的试点研究中确定 没有PCA诊断的年轻AA男性抗TAA自身抗体和肿瘤的血清水平升高 与具有PCA的AA男性相比，外泌体蛋白质。我们的目标是识别和验证新颖的血清 可以针对AA男性量身定制以增强PCA的血清学诊断，监测疾病的生物标志物 进展并指导个性化疗法。