Analysis of differentially expressed genes and drug targets based on preoperative and postoperative muscle tissue of obese patients with Roux-en-Y gastric bypass

Objective To analyze effect of expression of muscle tissue of obese patients with Roux-en-Y gastric bypass(RYGB), and to explore potential therapeutic targets for obesity.

Methods The dataset GSE16164 was downloaded from the Gene Expression Omnibus (GEO) database, thereby obtaining differentially expressed genes in muscle tissue of obese patients after RYGB. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) were performed to analyze biological functions and pathways. Enrichment analysis and immune cell infiltration analysis were performed to construct target-compound interaction network, key targets were screened out, and potential drug candidates for obesity treatment were found out by using CMap database.

Results There were 74 differentially expressed genes screened in the dataset GSE16164, including 30 up-regulated genes and 44 down-regulated genes. The gene enrichment analysis showed that dataset GSE16164 was mainly involved in 8 gene ontology functions, such as mRNA processing, RNA splicing, regulation of mRNA processing, regulation of RNA splicing, and so forth. KEGG pathway enrichment suggestedthat the dataset GSE161643 was enriched in pathway of herpes simplex virus 1 infection. There were no significant differences in the matrix component score and immune component score of muscle tissue samples after RYGB operation compared with that before RYGB (P>0.05). A total of 10 key targets were screened by target-compound interaction network, including UBC, CDK1, ERBB2, CDK2, CHEK2, CDC25A, ERBB3, SHC1, CHEK1 and BTRC. A total of 9 small molecular compounds targeted on UBC, CDK1, and ERBB2 were screened out in CMap database, which were clopidogrel, BNTX, cymarin, levofloxacin, SID-26681509, ezetimibe, isoeugenol, wortmannin, and PSB-06126.

Conclusion There are significant differences in gene expressions of skeletal muscle tissue of obese patients with RYGB postoperatively compared with before RYGB operation. These differences maybe serve as potential pharmacological targets for the therapeutic agents of obesity.