Integrative proteogenomic profiling of high-risk prostate cancer samples from Chinese patients indicates metabolic vulnerabilities and diagnostic biomarkers

Nat Cancer. 2024 Sep;5(9):1427-1447. doi: 10.1038/s43018-024-00820-2. Epub 2024 Sep 6.

Authors

Baijun Dong^#^{1

2}, Jun-Yu Xu^#^{3

4}, Yuqi Huang^#⁵, Jiacheng Guo^#⁶, Qun Dong^#⁷, Yanqing Wang^#¹, Ni Li⁶, Qiuli Liu⁸, Mingya Zhang⁵, Qiang Pan⁶, Hanling Wang⁶, Jun Jiang⁸, Bairun Chen⁷, Danqing Shen⁷, Yiming Ma⁷, Linhui Zhai^{5

9}, Jian Zhang¹⁰, Jing Li¹¹, Wei Xue¹², Minjia Tan^{13

14}, Jun Qin^{15

16}

Affiliations

¹ Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
² Department of Urology, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China.
³ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China. jyxu@simm.ac.cn.
⁴ Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Guangdong, China. jyxu@simm.ac.cn.
⁵ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
⁶ CAS Key Laboratory of Tissue Microenvironment and Tumor, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
⁷ Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
⁸ Department of Urology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, China.
⁹ Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
¹⁰ State Key Laboratory of Oncogenes and Related Genes, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
¹¹ Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. jing.li@sjtu.edu.cn.
¹² Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. xuewei@renji.com.
¹³ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China. mjtan@simm.ac.cn.
¹⁴ Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Guangdong, China. mjtan@simm.ac.cn.
¹⁵ CAS Key Laboratory of Tissue Microenvironment and Tumor, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China. qinjun@sibs.ac.cn.
¹⁶ Jinfeng Laboratory, Chongqing, China. qinjun@sibs.ac.cn.

^# Contributed equally.

PMID: 39242942
DOI: 10.1038/s43018-024-00820-2

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.

MeSH terms

Aged
Biomarkers, Tumor* / blood
Biomarkers, Tumor* / genetics
China
East Asian People / genetics
Gene Expression Regulation, Neoplastic
Hepatocyte Nuclear Factor 3-alpha* / genetics
Hepatocyte Nuclear Factor 3-alpha* / metabolism
Humans
Male
Middle Aged
Phosphorylation
Prognosis
Prostatic Neoplasms* / diagnosis
Prostatic Neoplasms* / genetics
Prostatic Neoplasms* / metabolism
Proteogenomics* / methods
Receptors, Androgen / genetics
Receptors, Androgen / metabolism

Substances

AR protein, human
Biomarkers, Tumor
FOXA1 protein, human
Hepatocyte Nuclear Factor 3-alpha
Receptors, Androgen

Abstract

MeSH terms

Substances

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