Integrative Proteogenomic Profiling of High-risk Prostate Cancer Samples from Chinese Patients Indicates Metabolic Vulnerabilities and Diagnostic Biomarkers

Overview

Journal Nat Cancer

Specialty Oncology

Date 2024 Sep 6

PMID 39242942

Authors

Baijun Dong

Jun-Yu Xu

Yuqi Huang

Jiacheng Guo

Qun Dong

Yanqing Wang

Ni Li

Qiuli Liu

Mingya Zhang

Qiang Pan

Hanling Wang

Jun Jiang

Bairun Chen

Danqing Shen

Yiming Ma

Linhui Zhai

Jian Zhang

Jing Li

Wei Xue

Minjia Tan

Jun Qin

Affiliations

Soon will be listed here.

Abstract

Prostate cancer (PCa) exhibits significant geoethnic disparities as reflected by distinct variations in the cancer genome and disease progression. Here, we perform a comprehensive proteogenomic characterization of localized high-risk PCa utilizing paired tumors and nearby tissues from 125 Chinese male patients, with the primary objectives of identifying potential biomarkers, unraveling critical oncogenic events and delineating molecular subtypes with poor prognosis. Our integrated analysis highlights the utility of GOLM1 as a noninvasive serum biomarker. Phosphoproteomics analysis reveals the crucial role of Ser331 phosphorylation on FOXA1 in regulating FOXA1-AR-dependent cistrome. Notably, our proteomic profiling identifies three distinct subtypes, with metabolic immune-desert tumors (S-III) emerging as a particularly aggressive subtype linked to poor prognosis and BCAT2 catabolism-driven PCa progression. In summary, our study provides a comprehensive resource detailing the unique proteomic and phosphoproteomic characteristics of PCa molecular pathogenesis and offering valuable insights for the development of diagnostic and therapeutic strategies.

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