Gender differences-based bioinformatics analysis to identify hub genes and key pathways in type 2 diabetes

Abstract

Type 2 diabetes (T2D) is a persistent medical condition characterized by insulin resistance and impaired insulin utilization. T2D is primarily observed in men and is strongly linked to obesity, which is considered a significant contributing factor to its onset. The underlying pathogenesis mechanism of T2D remains uncertain concerning potential sex differences. This study aimed to examine the differentially expressed genes (DEGs) and signaling pathways between males and females with T2D.For analysis of differentially expressed genes in this study, GSE86473 dataset was obtained from the NCBI's Gene Expression Omnibus (GEO). Utilizing Enrichr, we performed pathway enrichment analysis and gene ontology. Protein-protein interactions and hub genes are extracted using Cytoscape. Network-Analyst was employed to investigate transcription factors and microRNAs, protein-drug interactions, and gene-disease relationships.We identified 51 DEGs in men and 237 DEGs in women. We determined the leading 20 pathways and 15 GO terms for each gender. In male subjects, the following 15 hub genes were discovered: LDHA, FLT1, IGFBP3, LILRB4, CSF2, IL1A, HLA-C, UBD, C1QB, HLA-DMA, HLA-DPB1, CFB, HLA-DRB1, HLA-A, and CXCL8. The following genes were identified for female subjects: CPA1, CPB1, CEL, PNLIP, CPA2, CELA3A, SYCN, PRSS3P2, CTRB1, AMY2A, CTRC, PNLIPRP1, PRSS1, HLA-DRB1, and HLA-DQB1. We determined six TF genes shared by both males and females: ATF1, IRF1, MAZ, SSRP1, TFDP1, and MXD3. Mir-124-3p, mir-107, mir-16-5p, mir-23b-3p, mir-27a-3p, mir-103a-3p, mir-155-5p, and mir-1-3p were confirmed as microRNAs shared by males and females in our study. We analyzed protein-drug interactions to investigate the potential effects of a particular drug on the activity of target proteins in the body.The results of these analyses provided insights into the molecular mechanisms underlying the diseases under study and identified potential drug targets for further investigation. The hub genes identified in this study may have varying roles in the disease progression mechanisms of T2D between males and females, and they could serve as potential targets for treatment or prognostic markers for both sexes.