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

基本信息

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
项目类别：
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

项目摘要

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.

提高非裔美国 (AA) 男性的早期前列腺癌 (PCa) 检测对于减少癌症发病率至关重要 PCa 死亡率的种族差异。 PCa的检测和管理主要依靠PSA筛查。尽管该测试的使用改善了 PCa 的早期诊断和治疗，其局限性在于特异性，特别是肥胖 AA 男性，需要补充性非侵入性方法加强早期 PCa 检测、监测疾病进展并评估治疗反应。这这些新方法的实施将取决于确定更具体和敏感的可以为 AA 男性量身定制的生物标志物。我们将使用免疫血清蛋白质组学方法，重点关注分析抗肿瘤相关抗原 (TAAs) 的血清自身抗体和 AA 中的血清外泌体白种人 (CC) PCa 患者。该项目填补了系统性免疫血清蛋白质组学缺乏的空白患有 PCa 的 AA 患者的生物标志物鉴定研究。它建立在我们的主要观察基础上，表明： 1) PCa血清含有与肿瘤应激生存相关的TAA的自身抗体，例如LEDGF/p75和 Survivin，可以作为炎症传感器和细胞氧化应激的增强状态（ASCOS）； 2) TAA微型阵列增强PCa患者的抗体检测并区分癌症和正常人群； 3) PCa 特异性 TAA 的定制微型阵列在增强功能方面最有效 PCa的免疫血清学诊断； 4) PCa患者血清中含有含有应激生存的外泌体 Survivin 和 PRDX3 等蛋白质； 5) 蛋白质谱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 患者的外泌体将产生新的生物标志物，用于增强早期 PCa 检测和管理，从而实施针对 AA 男性的循证干预措施。目标目的是：1) 使用免疫蛋白质组学分析 AA 和 CC PCa 患者血清中的抗 TAA 抗体，定制TAA微型阵列； 2) 分析 AA 和 CC PCa 血清中肿瘤来源的外泌体蛋白通过蛋白质组学方法对患者进行治疗； 3) 在比较病例对照试点研究中确定是否未诊断出 PCa 的年轻 AA 男性的抗 TAA 自身抗体和肿瘤源性抗体的血清水平升高外泌体蛋白，与患有 PCa 的 AA 男性相比。我们的目标是识别和验证新型血清可以为 AA 男性量身定制的生物标志物，以增强 PCa 的血清学诊断、监测疾病进展，并指导个性化治疗。