Integrative bioinformatics analysis to screen key genes and signalling pathways related to ferroptosis in obesity

Abstract

ABSTRACT Ferroptosis is closely associated with the development of disease in the body. However, there are few studies on ferroptosis-related genes (FRGs) in obesity. Therefore, key genes and signalling pathways related to ferroptosis in obesity were screened. Briefly, the RNA sequencing data of obesity and the non-obesity human samples and 259 FRGs were downloaded from GEO database and FerrDb database, respectively. The obesity-related module genes were firstly screened by weighted gene co-expression network analysis (WGCNA) and crossed with differentially expressed genes (DEGs) of obesity/normal samples and FRGs to obtain obesity-ferroptosis related (OFR) DEGs. Then, key genes were screened by PPI network. Next, the correlation of key genes and differential immune cells between obesity and normal samples were further explored by immune infiltration analysis. Finally, microRNA (miRNA)-messenger RNA (mRNA), transcription factor (TF)-mRNA networks and drug-gene interaction networks were constructed. As a result, 17 OFR DEGs were obtained, which mainly participated in processes such as lipid metabolism or adipocyte differentiation. The 4 key genes, STAT3, IL-6, PTGS2, and VEGFA, constituted the network. M2 macrophages, T cells CD8, mast cells activated, and T cells CD4 memory resting had significant differences between obesity and normal samples. Moreover, 51 miRNAs and 164 drugs were predicted for 4 key genes. All in all, this study has screened 4 FRGs, including IL-6, VEGFA, STAT3, and PTGS2, in obesity patients.