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Roux-en-Y胃旁路术前后肥胖症患者肌肉组织的差异表达基因和药物靶点分析

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

    摘要
  • 摘要:
    目的 分析Roux-en-Y胃旁路术(RYGB)对肥胖症患者肌肉组织基因表达的影响, 探讨肥胖症的潜在治疗靶点。
    方法 筛选GEO数据库，下载GSE161643数据集，获得RYGB术后肥胖症患者肌肉组织的差异表达基因，进行富集分析和免疫细胞浸润分析，构建靶点-化合物相互作用网络，筛选出关键靶点，并利用CMap数据库寻找可治疗肥胖症的潜在候选药物。
    结果 本研究共筛选出RYGB术后肌肉组织差异表达基因74个，其中上调基因30个、下调基因44个。基因集富集分析结果提示，GSE161643数据集富集于mRNA加工、RNA剪接、mRNA加工的调控、RNA剪接的调控等8个GO功能。京都基因与基因组百科全书(KEGG)富集分析显示，GSE161643数据集富集于单纯疱疹病毒1型感染通路。RYGB术后，肌肉组织样本的基质成分评分、免疫成分评分与RYGB术前比较，差异均无统计学意义(P>0.05)。靶点-化合物相互作用网络共筛选出10个关键靶点，分别为UBC、CDK1、ERBB2、CDK2、CHEK2、CDC25A、ERBB3、SHC1、CHEK1和BTRC。CMap数据库共筛选出共同作用于UBC、CDK1、ERBB2的小分子化合物9个，分别为氯吡格雷、BNTX、香豆素、左氧氟沙星、SID-26681509、依折麦布、异丁香酚、渥曼青霉素和PSB-06126。
    结论 与RYGB术前相比，肥胖症患者RYGB术后的肌肉组织基因表达存在显著差异，这些差异可能成为治疗肥胖症的潜在药物靶点。

     

    Abstract:
    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.

     

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