<b>Identification of key genes related to oxidative stress in Type 2 Diabetes Mellitus and prediction of potential traditional Chinese medicine based on comprehensive bioinformatics analysis</b>

Background: The oxidative stress (OS) process can significantly impact diabetes, especially type 2 diabetes mellitus (T2DM). This study aimed to identify OS-related genes which may play important roles in T2DM and to screen for traditional Chinese medicine (TCM) that could be applied. Methods: The GSE23343 data set was downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified between healthy and T2DM patients. Then, weighted gene co-expression network analysis (WGCNA) was applied. The modules which showed high correlation with clinical traits were selected and the core genes in the modules were identified. OS-related genes were obtained from searching the GeneCards database. The overlapping set of DEGs, WGCNA modular genes, and OS-related genes yielded hub genes in OS-related T2DM. These genes were examined in GSE15653 dataset. Potential TCMs were found by mapping the hub genes with the Coremine Medical database. Results: A total of 394 DEGs (136 up-regulated and 258 down-regulated DEGs.) were identified in the GSE23343 cohort. WGCNA results showed that the turquoise module (cor=–0.56, P=0.02) and the brown module (cor=0.66, P=0.004) were the most negatively and positively correlated with T2DM, respectively, and 1016 key keys were identified from the two key modules. We identified three up-regulated hub genes (IL33, S100A8, GOLM1) and three down-regulated hub genes (SNRNP70, HGFAC, GOLM1), which performed well in distinguishing T2DM from healthy samples (AUC>0.8). In addition, six plants used in TCM are predicted to affect expression of these genes. Conclusion: IL33, S100A8, GOLM1, SNRNP70, HGFAC, and OSGIN1 are key biomarker genes in OS-related T2DM. TCMs could supplement current therapies by affecting expressions of these genes.