基于生物信息学的十二指肠腺瘤核心致病基因及其靶向治疗中药活性成分筛选

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摘要目的: 利用生物信息学方法对十二指肠腺瘤（duodenal adenoma, DA）的核心致病基因进行筛选和分析，挖掘潜在的可用于靶向治疗DA的中药活性成分。方法: 从GEO数据库下载DA数据集（Accession No. GSE102208），运用GEO2R筛选差异表达基因（differentially expressed genes, DEGs），应用DAVID数据库对DEGs进行GO及KEGG富集分析，采用STRING数据库对DEGs进行蛋白质相互作用网络（proteinprotein interaction, PPI）分析，利用Cytoscape获取DA核心致病基因，通过CTD数据库挖掘靶向作用于核心致病基因的中药活性成分。结果：筛选获得DA患者与健康者十二指肠组织显著性DEGs共373个，其中270个上调，103个下调。主要涉及胆固醇稳态、胆固醇流出、脂蛋白合成、三酰甘油稳态等生物学过程，富集于PI3kAkt、PPAR、碳水化合物消化吸收、蛋白质消化吸收、脂肪消化吸收、胆汁分泌等信号通路。筛选出载脂蛋白B（ApoB）、表皮细胞生长因子（EGF）、载脂蛋白A1（ApoA1）、葡萄糖转运蛋白2（SLC2A2）、麦芽糖酶糖化酶（MGAM）等10个关键基因；进一步分析获得可能用于治疗DA的潜在靶向中药活性成分，包括白藜芦醇、槲皮素、人参皂苷、姜黄素、雷公藤甲素等。结论：基于公共数据库可以筛选与DA发生发展密切相关的基因靶点，并挖掘到潜在的可用于DA靶向治疗的中药活性成分。

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关键词 ：十二指肠腺瘤, 差异表达基因, 生物信息学, 核心致病基因, 靶向药物

Abstract：Objective: To screen and analyze the core pathogenic genes of Duodenal Adenoma （DA） by using bioinformatics methods, and discover the active components of Chinese materia medica that may be used for targeted treatment of DA. Methods: DA data set GSE102208 was downloaded from GEO database, GEO2R was used to screen differentially expressed genes （DEGs）, DAVID database was used to perform GO and KEGG enrichment analysis of DEGs, STRING database was used for proteinprotein interaction（PPI）analysis, and Cytoscape was applied to obtain DA core pathogenic genes. The CTD database was used to obtain targeted Chinese medicine active components that act on core pathogenic genes. Results: A total of 373 differentially expressed genes between DA patients and normal people were screened, including 270 upregulated genes and 103 downregulated ones, which were mainly involved in cholesterol import, cholesterol homeostasis, cholesterol efflux, lipoprotein biosynthetic process, triglyceride homeostasis and other biological processes and enriched in signaling pathways including PI3kAKT, PPAR, carbohydrate digestion and absorption, protein digestion and absorption, fat digestion and absorption, and bile secretion. Ten key genes including ApoB, EGF, ApoA1, SLC2A2, MGAM were screened out. Further analysis revealed potential targeted Chinese medicine active components including Resveratrol, Quercetin, Ginsenoside, Curcumin, Tripterygium Wilfordii. Conclusion: Public databases may be used to screen the gene targets closely related to the occurrence and development of DA, and explore the active components of Chinese materia medica that may be used for DA targeted therapy.

收稿日期: 2020-10-22

基金资助:国家自然科学基金资助项目（81703920）；湖南省自然科学基金资助项目（2019JJ50442）；湖南省教育厅科学研究项目（19C1426）；湖南省大学生研究性学习和创新性实验计划项目（201908, 20202578）

通讯作者: 宋厚盼（通讯作者），副教授，硕士生导师，E-mail: hpsong2015@126.com

作者简介: 冯瑶（1999—），女，2017级口腔医学专业学生

引用本文:

冯瑶1,2，陈新怡1,3，宋厚盼1,3，刘涛1,3，杨焘2，刘恒铭2，仇婧玥1,3，曾梅艳3. 基于生物信息学的十二指肠腺瘤核心致病基因及其靶向治疗中药活性成分筛选[J]. 江苏大学学报:医学版, 2021, 31(02): 158-165. FENG Yao1,2， CHEN Xinyi1,3， SONG Houpan1,3， LIU Tao1,3， YANG Tao2，LIU Hengming2， QIU Jingyue1,3，.

Bioinformatics study on core pathogenic genes of duodenal adenoma and active components of Chinese materia medica for targeted therapy

. Journal of Jiangsu University(Medicine Edition), 2021, 31(02): 158-165.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2021/V31/I02/158

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