Immunoseroproteomics in Prostate Cancer: Focus on Health Disparities

改善非洲裔美国人（AA）男性的早期前列腺癌（PCa）检测对于减少 PCa死亡率的种族差异。前列腺癌的检测和管理主要依赖于PSA筛查。而 该试验的使用改善了PCa的早期诊断和管理， 特异性，特别是肥胖AA男性，需要补充的非侵入性方法， 增强早期PCa检测、监测疾病进展和评估治疗反应。的 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， 分析AA中针对肿瘤相关抗原（TAA）和血清外泌体的血清自身抗体， 高加索（CC）PCa患者。该项目填补了缺乏系统的免疫血清蛋白质组学的差距 在患有PCa的AA患者中进行生物标志物鉴定的研究。它建立在我们的主要观察结果之上，这些观察结果表明： 1)PCa血清含有涉及肿瘤应激存活的TAA的自身抗体，如LEDGF/p75和 存活素，并可作为炎症和细胞氧化应激增强状态的传感器 （ASCOS）; 2）TAA微阵列增强PCa患者中的抗体检测并区分癌症 和正常人群; 3）定制的PCA特异性TAA微型阵列在增强 PCa免疫血清学诊断; 4）PCa患者血清具有含有应激存活的外来体 蛋白质如Survivin和PRDX3;和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抗体和 AA和CC PCa患者中的外来体将产生用于增强早期PCa检测的新生物标志物， 管理，导致实施针对AA男性的循证干预措施。目标 1）使用免疫蛋白质组学分析来自AA和CC PCa患者的血清中的抗-TAA抗体， 定制的TAA微型阵列; 2）分析来自AA和CC PCa的血清中的肿瘤来源的外来体蛋白 患者的蛋白质组学方法;和3）在一项比较性病例对照初步研究中确定， 没有PCa诊断的年轻AA男性血清抗TAA自身抗体和肿瘤源性抗体水平升高， 外泌体蛋白，相比AA男性与PCa。我们的目标是鉴定和验证新型血清 生物标志物，可以定制AA男性，以加强PCa的血清学诊断，监测疾病 发展，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.