Proteogenomic Characterization of Human Early-Onset Gastric Cancer

Cancer Cell. 2019 Jan 14;35(1):111-124.e10. doi: 10.1016/j.ccell.2018.12.003.

Abstract

We report proteogenomic analysis of diffuse gastric cancers (GCs) in young populations. Phosphoproteome data elucidated signaling pathways associated with somatic mutations based on mutation-phosphorylation correlations. Moreover, correlations between mRNA and protein abundances provided potential oncogenes and tumor suppressors associated with patient survival. Furthermore, integrated clustering of mRNA, protein, phosphorylation, and N-glycosylation data identified four subtypes of diffuse GCs. Distinguishing these subtypes was possible by proteomic data. Four subtypes were associated with proliferation, immune response, metabolism, and invasion, respectively; and associations of the subtypes with immune- and invasion-related pathways were identified mainly by phosphorylation and N-glycosylation data. Therefore, our proteogenomic analysis provides additional information beyond genomic analyses, which can improve understanding of cancer biology and patient stratification in diffuse GCs.

Keywords: cancer subtypes; correlation between mRNA and protein abundance changes; correlation between mutation and phosphorylation; diffuse gastric cancer; proteogenomics; somatic nonsynonymous mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Exome Sequencing / methods
  • Female
  • Gene Regulatory Networks*
  • Glycosylation
  • Humans
  • Male
  • Mutation*
  • Phosphorylation
  • Protein Interaction Maps
  • Proteogenomics / methods*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism*
  • Survival Analysis