Proteome-centric cross-omics characterization and integrated network analyses of triple-negative breast cancer

• Published in: Cell reports (Cambridge) 2022-03, Vol.38 (9), p.110460-110460, Article 110460
• Main Authors: Gong, Tian-Qi, Jiang, Yi-Zhou, Shao, Chen, Peng, Wen-Ting, Liu, Ming-Wei, Li, Da-Qiang, Zhang, Ben-Yu, Du, Peng, Huang, Yin, Li, Fei-Fei, Li, Mu-Yun, Han, Zhao-Lian, Jin, Xi, Ma, Ding, Xiao, Yi, Yang, Peng-Yuan, Qin, Jun, Shao, Zhi-Ming, Zhu, Weimin
• Format: Article
• Language: English
• Subjects: drug target; Genome; Humans; integrated network analysis; integrative multi-omics analysis; Proteome - genetics; proteomic subtyping; Proteomics; TNBC molecular library; Transcriptome; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - metabolism; triple-negative breast cancer (TNBC)
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.110460

We report a comprehensive proteomic study of a 90-case cohort of paired samples of triple-negative breast cancer (TNBC) in quantification, phosphorylation, and DNA-binding capacity. Four integrative subtypes (iP-1–4) are stratified on the basis of global proteome and phosphoproteome, each of which exhibits distinct molecular and pathway features. Scaffold and co-expression network analyses of three proteomic datasets, integrated with those from genome and transcriptome of the same cohort, reveal key pathways and master regulators that, characteristic of TNBC subtypes, play important regulatory roles within and between scaffold sub-structures and co-expression communities. We find that NAE1 is a potential drug target for subtype iP-1, and a series of key molecules in fatty acid metabolism, such as AKT1/FASN, are plausible targets for subtype iP-2. Libraries of proteins, pathways and networks of TNBC provide a valuable molecular infrastructure for further clinical exploration and in-depth studies of the molecular mechanisms of the disease. [Display omitted] •Multi-omics profile of a 90-case cohort of TNBCs•Proteomics reveal four TNBC subtypes related to clinical and molecular features•Integrated multi-omics analyses result in molecular machinery and insights of TNBC•Integrated multi-omics analysis indicates potential drug targets within subtypes Gong et al. provide integrative proteomic characterization of triple-negative breast cancer (TNBC) in 90 patients, which identifies four integrative subtypes related to clinical and molecular features, and conduct integrated multi-omics network analysis, which helps to nominate NAE1 and FASN/AKT1 as potential prognostic drug targets.