Identification of MEDAG as a Hub Candidate Gene in the Onset and Progression of Type 2 Diabetes Mellitus by Comprehensive Bioinformatics Analysis

Objectives: We conducted the present study to identify novel hub candidate genes in the pathogenesis of type 2 diabetes mellitus (T2DM) and provide potential biomarkers or therapeutic targets for dealing with the disease.

Methods: We conducted weighted gene coexpression network analysis on a series of the expression profiles of the pancreas islet of T2DM patients obtained from the Gene Expression Omnibus database to construct a weighted coexpression network. After dividing genes into separated coexpression modules, we identified a T2DM-related module using Pearson's correlation analysis. Then, hub genes were identified from the T2DM-related module using the Maximal Clique Centrality method and validated by correlation analysis with clinical traits, differentially expressed gene analysis, validation in other datasets, and single-gene gene set enrichment analysis (GSEA).

Results: Genes were divided into 16 coexpression modules, and one module was identified as a T2DM-related module. Four hub candidate genes were identified, and MEDAG was a novel hub candidate gene. The expression level of MEDAG was positively correlated with hemoglobin A1c (HbA1c) and was evidently overexpressed in the pancreas islet tissue of T2DM patients compared with normal control. Analyses on two other datasets supported the results. GSEA verified that MEDAG plays essential roles in T2DM.

Conclusions: MEDAG is a novel hub candidate of T2DM, and its irregular expression in the pancreas islet plays vital roles in the pathogenesis of T2DM. MEDAG is a potential target of intervention in the future for the treatment of T2DM.