ADAR expression and copy number variation in patients with advanced gastric cancer

BMC Gastroenterol. 2020 May 14;20(1):152. doi: 10.1186/s12876-020-01299-8.

Abstract

Background: Gastric cancer (GC) is a world health problem and it is the third leading cause of cancer deaths worldwide. The current practice for prognosis assessment in GC is based on radiological and pathological criteria and they may not result in an accurate prognosis. The aim of this study is to evaluate expression and copy number variation of the ADAR gene in advanced GC and clarify its correlation with survival and histopathological characteristics.

Methods: Forty two patients with stage III and IV GC were included in this study. ADAR gene expression and copy number variation were measured by real-time PCR and Quantitative multiplex fluorescent-PCR, respectively. Survival analysis performed based on the Kaplan-Meier method and Mantel-Cox test.

Results: ADAR mRNA was significantly overexpressed in the tumor tissues when compared to the adjacent normal tissues (p < 0.01). Also, ADAR expression level in stage IV was higher than stage III. 40% of patients showed amplification in ADAR gene and there was a positive correlation between ADAR copy number and expression. Increased ADAR expression was clearly correlated with poorer survival outcomes and Mantel-Cox test showed statistically significant differences between low and high expression groups (p < 0.0001). ADAR overexpression and amplification were significantly associated with metastasis, size and stage of tumor.

Conclusions: Together, our data indicate that amplification leads to over expression of ADAR and it could be used as a prognostic biomarker for disease progression, especially for the metastatic process in GC.

Keywords: ADAR gene; Amplification; Gastric cancer; Overexpression; Prognosis.

Publication types

  • Evaluation Study

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality*
  • Adenocarcinoma / pathology
  • Adenosine Deaminase / metabolism*
  • Aged
  • Biomarkers, Tumor / genetics
  • DNA Copy Number Variations / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • RNA-Binding Proteins / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality*
  • Stomach Neoplasms / pathology
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • RNA-Binding Proteins
  • ADAR protein, human
  • Adenosine Deaminase