Prognostic Epstein-Barr Virus (EBV) miRNA biomarkers for survival outcome in EBV-associated epithelial malignancies: Systematic review and meta-analysis

PLoS One. 2022 Apr 18;17(4):e0266893. doi: 10.1371/journal.pone.0266893. eCollection 2022.

Abstract

Background: The EBV-associated epithelial tumours consist 80% of all EBV-associated cancer, where the nasopharyngeal cancer (NPC) and EBV-associated gastric carcinoma (EBVaGC) are considered as the most frequent EBV-associated epithelial tumours. It has been shown that the BART-encoded miRNAs are abundantly expressed in EBV-associated epithelial tumours, hence, these miRNAs may serve as diagnostic and prognostic biomarkers for EBV-associated epithelial tumours. Therefore, the purpose of this systematic review and meta-analysis is to assess these EBV miRNAs as prognostic biomarkers for NPC and GC.

Method: This systematic review was developed based on PRISMA guidelines and utilizing PubMed, Web of Science, Scopus, Cochrane, and Google scholar databases. The retrieved articles were thoroughly screened in accordance with the selection criteria. The hazard ratio (HR) and 95% confidence interval (CI) for patient survival outcomes were used to evaluate EBV miRNA expression levels. To assess the risk of bias, funnel plot symmetry and Egger's bias test were employed.

Result: Eleven studies met the selection criteria for inclusion, and four were included in the meta-analysis. Most of the articles considered in this study were from China, with one study from South Korea. The overall pooled effect size estimation (HR) for upregulated EBV miRNAs was 3.168 (95% CI: 2.020-4.969), demonstrating that upregulated EBV miRNA expression enhanced the mortality risk in NPC and GC patients by three times.

Conclusion: To the best of our knowledge, this is the first meta-analysis that investigates the significance of EBV miRNAs as prognostic biomarkers in NPC and GC patients. The pooled effect estimates of HR of the various studies revealed that higher EBV miRNA expression in NPC and GC may result in a worse survival outcome. To assess the clinical significance of EBV miRNAs as prognostic biomarkers, larger-scale prospective studies are needed.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Epstein-Barr Virus Infections* / genetics
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / metabolism
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Nasopharyngeal Carcinoma / genetics
  • Nasopharyngeal Neoplasms* / pathology
  • Prognosis

Substances

  • Biomarkers
  • MicroRNAs

Grants and funding

This work was supported by Ministry of Higher Education Malaysia for Fundamental Research Grant Scheme with Project Code: FRGS/1/2018/SKK08/USM/02/1 to CYY (corresponding author). The funder had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study.