Immunoseroproteomics in Prostate Cancer: Focus on Health Disparities

改善非裔美国人(AA)男性的早期前列腺癌(PCA)检测是减少 前列腺癌死亡率的种族差异。前列腺癌的检测和管理主要依靠PSA筛查。而当 这项测试的使用改善了PCa的早期诊断和处理，其在以下方面的局限性 特异性，特别是在肥胖的AA男性中，需要补充的非侵入性方法来治疗 加强早期PCA检测，监测疾病进展，并评估治疗反应。这个 这些新方法的实施将取决于确定更具体和更敏感的 可以为AA男性量身定做的生物标记物。我们将使用一种免疫蛋白质组学方法，重点是 再生障碍性贫血和慢性再生障碍性贫血患者血清抗肿瘤相关抗原(TAAs)自身抗体和血清外切体的分析 高加索人(CC)前列腺癌患者。该项目填补了缺乏系统免疫蛋白质组学的空白 再生障碍性贫血患者前列腺癌的生物标志物鉴定研究。它建立在我们的主要观察结果的基础上，表明： 1)PCa血清中含有与肿瘤应激生存有关的TAAs自身抗体，如LEDGF/p75和 Survivin，可作为炎症和细胞氧化应激增强状态的感受器 (ASCOS)；2)TAA微阵列增强PCa患者的抗体检测并区分癌症 和正常人群；3)定制的PCA特异性TAA微阵列最有效地增强 前列腺癌的免疫血清学诊断；4)前列腺癌患者血清中含有应激存活的外显子 Survivin和PRDX3等蛋白质；以及5)蛋白质谱或水平可能存在种族差异 血清外切体。我们的中心假设是血清抗TAA抗体和 AA和CC PCa患者的外切体将产生新的生物标志物，以加强早期PCa检测和 管理，导致实施针对再生障碍性贫血男子的循证干预。目标 1)用免疫蛋白质组学方法分析AA和CC PCa患者血清中的ANFI-TAA抗体 定制的TAA微阵列；2)分析AA和CC PCa血清中肿瘤来源的胞外蛋白 通过蛋白质组学方法对患者进行研究；以及3)在比较病例对照先导性研究中确定 未诊断为前列腺癌的年轻AA患者血清抗TAA自身抗体水平升高，肿瘤来源 胞外体蛋白，与患有前列腺癌的AA患者相比。我们的目标是鉴定和验证新的血清 可为AA患者量身定做的生物标记物，以提高对PCa的血清学诊断，监测疾病 进展，并指导个性化治疗。

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.