Integrated Proteomic and Genomic Analysis of Gastric Cancer Patient Tissues

J Proteome Res. 2015 Dec 4;14(12):4995-5006. doi: 10.1021/acs.jproteome.5b00827. Epub 2015 Oct 20.

Abstract

V-erb-b2 erythroblastic leukemia viral oncogene homologue 2, known as ERBB2, is an important oncogene in the development of certain cancers. It can form a heterodimer with other epidermal growth factor receptor family members and activate kinase-mediated downstream signaling pathways. ERBB2 gene is located on chromosome 17 and is amplified in a subset of cancers, such as breast, gastric, and colon cancer. Of particular interest to the Chromosome-Centric Human Proteome Project (C-HPP) initiative is the amplification mechanism that typically results in overexpression of a set of genes adjacent to ERBB2, which provides evidence of a linkage between gene location and expression. In this report we studied patient samples from ERBB2-positive together with adjacent control nontumor tissues. In addition, non-ERBB2-expressing patient samples were selected as comparison to study the effect of expression of this oncogene. We detected 196 proteins in ERBB2-positive patient tumor samples that had minimal overlap (29 proteins) with the non-ERBB2 tumor samples. Interaction and pathway analysis identified extracellular signal regulated kinase (ERK) cascade and actin polymerization and actinmyosin assembly contraction as pathways of importance in ERBB2+ and ERBB2- gastric cancer samples, respectively. The raw data files are deposited at ProteomeXchange (identifier: PXD002674) as well as GPMDB.

Keywords: Chromosome-centric Human Proteome Project; EGFR; ERBB2; GRB2; RNA-Seq; gastric cancer patient tissues.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Cell Line, Tumor
  • Gene Expression Profiling
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Receptor, ErbB-2 / metabolism*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism*

Substances

  • ERBB2 protein, human
  • Receptor, ErbB-2