Integrative Proteomics in Prostate Cancer Uncovers Robustness Against Genomic and Transcriptomic Aberrations During Disease Progression

Nat Commun. 2018 Mar 21;9(1):1176. doi: 10.1038/s41467-018-03573-6.

Abstract

To understand functional consequences of genetic and transcriptional aberrations in prostate cancer, the proteomic changes during disease formation and progression need to be revealed. Here we report high-throughput mass spectrometry on clinical tissue samples of benign prostatic hyperplasia (BPH), untreated primary prostate cancer (PC) and castration resistant prostate cancer (CRPC). Each sample group shows a distinct protein profile. By integrative analysis we show that, especially in CRPC, gene copy number, DNA methylation, and RNA expression levels do not reliably predict proteomic changes. Instead, we uncover previously unrecognized molecular and pathway events, for example, several miRNA target correlations present at protein but not at mRNA level. Notably, we identify two metabolic shifts in the citric acid cycle (TCA cycle) during prostate cancer development and progression. Our proteogenomic analysis uncovers robustness against genomic and transcriptomic aberrations during prostate cancer progression, and significantly extends understanding of prostate cancer disease mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Citric Acid Cycle / genetics
  • DNA Methylation
  • Disease Progression
  • Gene Dosage
  • Gene Expression Regulation, Neoplastic*
  • Genome-Wide Association Study
  • Genomics
  • Humans
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Prostate / metabolism
  • Prostate / pathology
  • Prostatic Hyperplasia / genetics*
  • Prostatic Hyperplasia / metabolism
  • Prostatic Hyperplasia / pathology
  • Prostatic Neoplasms, Castration-Resistant / genetics*
  • Prostatic Neoplasms, Castration-Resistant / metabolism
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transcriptome*

Substances

  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Messenger