Abstract A057: Integrated proteogenomics uncovers ancestry-specific and shared molecular drivers in localized prostate cancer

作者：Cara C. Schafer, Tamara Abulez, Xijun Zhang, Kun-Lin Ho, Jiji Jiang, Denise Young, Jesse Fox, Kelly A. Conrads, Brian L. Hood, Gauthaman Sukumar, Darryl Nousome, Praveen-Kumar Raj-Kumar, Mariano Russo, Ayesha A. Shafi, Xiaofeng A. Su, Albert Dobi, Amina Yusuf Ali, Sally Elsamanoudi, Jennifer Cullen, William D. Figg, György Petrovics, Clifton L. Dalgard, Matthew D. Wilkerson, Nicholas W. Bateman, Thomas P. Conrads, Isabell A. Sesterhenn, Leigh Ellis, Craig D. Shriver, Gregory T. Chesnut, Shyh‐Han Tan · 发表于：Cancer Research · 年份：2026 · DOI：10.1158/1538-7445.prostateca26-a057 · 研究领域：Cardiovascular Health and Risk Factors、Cancer Genomics and Diagnostics、Prostate Cancer Treatment and Research

Abstract Background: Black men experience higher incidence and mortality rates from prostate cancer, yet the molecular drivers of outcome disparities are not clearly defined. We performed a multi-omics analysis of localized PCa in the equal access Military Health System to identify ancestry-associated biological differences and prognostic markers. Methods: We analyzed tumors from 112 patients (57 Black, 55 White) using whole genome sequencing, quantitative proteomics, and phosphoproteomics. To identify ancestry-associated differences, we leveraged gene set enrichments from over-representation analyses and then used Multi-Omics Gene-Set Analysis (MOGSA) to determine the contribution of multi-omics features to these enrichments. Integrative clustering using iClusterBayes was applied to define molecular subtypes based on shared variation across multi-omics data. Germline regulation of the proteome was assessed via eQTL analyses. Prognostic significance was evaluated with Cox proportional hazards models (adjusted for age, PSA, and percent African ancestry); and ancestry-specific biomarker panels were validated using Kaplan–Meier and AUC analyses. Results: Black patients displayed higher genomic variability, stronger androgen response, fatty-acid metabolism, and EMT. White patients were enriched for DNA repair gene deletions, MYC/E2F signaling, mTORC1 activity, and cell-cycle progression. Phosphoproteomics revealed ancestry-specific kinase dependencies, with CK2α and CHEK2 activit...