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

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.