High RhCG expression predicts poor survival and promotes migration and proliferation of gastric cancer via keeping intracellular alkaline

Exp Cell Res. 2020 Jan 15;386(2):111740. doi: 10.1016/j.yexcr.2019.111740. Epub 2019 Nov 19.

Abstract

Advanced gastric cancer (GC) is aggressive with a high mortality rate. Rhesus family, C glycoprotein (RhCG) participates in tumor progression in many cancers, however its function in GC is still unknown. Here, we showed that RhCG was overexpressed in GC tissues at mRNA (P = 0.036) and protein levels (P < 0.05) compared with normal tissues. High RhCG level was correlated with poor differentiation (P = 0.037), TNM stage (P < 0.001), high HER-2 level (P = 0.018) and worse prognosis (P < 0.001). Cox proportional hazard model indicated that RhCG level was an independent prognostic biomarker. RhCG knockdown significantly decreased pHi and impeded tumor cellular proliferation, migration and invasion and repressed β-catenin and c-myc expression in GC cells. Moreover, GC cells with high RhCG level had reduced oxaliplatin efficacy suggesting a role for RhCG as a therapeutic target for GC. Our findings revealed a function of RhCG in cancer pathogenesis, invasion and metastasis in human GC. We suggest that RhCG act may as a novel prognostic indicator and a therapeutic target for gastric adenocarcinoma.

Keywords: C glycoprotein; Drug-sensitivity; Gastric cancer; Intracellular pH; Prognosis; Rhesus family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Cation Transport Proteins / antagonists & inhibitors
  • Cation Transport Proteins / genetics*
  • Cation Transport Proteins / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hydrogen-Ion Concentration
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Lymphatic Metastasis
  • Male
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism
  • Middle Aged
  • Neoplasm Staging
  • Oxaliplatin / therapeutic use
  • Prognosis
  • Proportional Hazards Models
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / metabolism
  • Signal Transduction
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • CTNNB1 protein, human
  • Cation Transport Proteins
  • MYC protein, human
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-myc
  • RHCG protein, human
  • beta Catenin
  • Oxaliplatin
  • ERBB2 protein, human
  • Receptor, ErbB-2