Optimizing miRNA-module diagnostic biomarkers of gastric carcinoma via integrated network analysis

PLoS One. 2018 Jun 7;13(6):e0198445. doi: 10.1371/journal.pone.0198445. eCollection 2018.

Abstract

Several microRNAs (miRNAs) have been suggested as novel biomarkers for diagnosing gastric cancer (GC) at an early stage, but the single-marker strategy may ignore the co-regulatory relationships and lead to low diagnostic specificity. Thus, multi-target modular diagnostic biomarkers are urgently needed. In this study, a Zsummary and NetSVM-based method was used to identify GC-related hub miRNAs and activated modules from clinical miRNA co-expression networks. The NetSVM-based sub-network consisting of the top 20 hub miRNAs reached a high sensitivity and specificity of 0.94 and 0.82. The Zsummary algorithm identified an activated module (miR-486, miR-451, miR-185, and miR-600) which might serve as diagnostic biomarker of GC. Three members of this module were previously suggested as biomarkers of GC and its 24 target genes were significantly enriched in pathways directly related to cancer. The weighted diagnostic ROC AUC of this module was 0.838, and an optimized module unit (miR-451 and miR-185) obtained a higher value of 0.904, both of which were higher than that of individual miRNAs. These hub miRNAs and module have the potential to become robust biomarkers for early diagnosis of GC with further validations. Moreover, such modular analysis may offer valuable insights into multi-target approaches to cancer diagnosis and treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Area Under Curve
  • Biomarkers, Tumor / genetics*
  • Cluster Analysis
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • MicroRNAs / metabolism*
  • ROC Curve
  • Sensitivity and Specificity
  • Stomach Neoplasms / diagnosis*
  • Support Vector Machine

Substances

  • Biomarkers, Tumor
  • MicroRNAs

Grants and funding

The authors’ work is funded by The National Major Scientific and Technological Special Project for “Significant New Drugs Development”(2017ZX09301059 to ZW), the National Natural Science Foundation of China (81673833 to JL, 81703947 to ZW) and The Natural Science Foundation of Hebei province (H2015206461 to FZ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.