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.
Copyright © 2019 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Antineoplastic Agents / therapeutic use
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Biomarkers, Tumor / genetics*
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Biomarkers, Tumor / metabolism
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Carcinoma, Hepatocellular / diagnosis
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Carcinoma, Hepatocellular / drug therapy
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Carcinoma, Hepatocellular / genetics*
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Carcinoma, Hepatocellular / mortality
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Cation Transport Proteins / antagonists & inhibitors
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Cation Transport Proteins / genetics*
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Cation Transport Proteins / metabolism
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Cell Line, Tumor
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Cell Movement / drug effects
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Cell Proliferation / drug effects
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Female
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Gene Expression Regulation, Neoplastic*
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Humans
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Hydrogen-Ion Concentration
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Liver Neoplasms / diagnosis
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Liver Neoplasms / drug therapy
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Liver Neoplasms / genetics*
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Liver Neoplasms / mortality
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Lymphatic Metastasis
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Male
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Membrane Glycoproteins / antagonists & inhibitors
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Membrane Glycoproteins / genetics*
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Membrane Glycoproteins / metabolism
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Middle Aged
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Neoplasm Staging
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Oxaliplatin / therapeutic use
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Prognosis
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Proportional Hazards Models
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / metabolism
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Receptor, ErbB-2 / genetics*
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Receptor, ErbB-2 / metabolism
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Signal Transduction
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beta Catenin / genetics
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beta Catenin / metabolism
Substances
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Antineoplastic Agents
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Biomarkers, Tumor
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CTNNB1 protein, human
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Cation Transport Proteins
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MYC protein, human
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Membrane Glycoproteins
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Proto-Oncogene Proteins c-myc
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RHCG protein, human
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beta Catenin
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Oxaliplatin
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ERBB2 protein, human
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Receptor, ErbB-2