基于生物信息学分析林奇综合征相关结直肠癌关键Hub基因的筛选与功能富集分析

doi:10.19586/j.2095-2341.2022.0122

生物技术进展 ›› 2023, Vol. 13 ›› Issue (2): 291-297.DOI: 10.19586/j.2095-2341.2022.0122

• 研究论文 • 上一篇

基于生物信息学分析林奇综合征相关结直肠癌关键Hub基因的筛选与功能富集分析

朱兴墅¹(), 黄军杰¹, 翁才明², 刘旺武², 陈永元², 陈惠燕², 赵虎²^,³, 王瑜²^,³, 林承志²^,³()

^1.福建中医药大学中西医结合学院，福州 350122
^2.福建医科大学福总临床医学院（第九〇〇医院），福州 350025
^3.中国人民解放军联勤保障部队第九〇〇医院，福州 350025

收稿日期:2022-07-01 接受日期:2022-08-18 出版日期:2023-03-25 发布日期:2023-04-07
通讯作者: 林承志
作者简介:朱兴墅 E-mail: 862379991@qq.com；
基金资助:
国家自然科学基金青年项目(82003002);福建省引导项目(2021Y0061);福建医科大学科研发展基金项目(2021QH1322)

Screening and Functional Enrichment Analysis of Key Hub Genes in Lynch Syndrome-associated Colorectal Cancer Based on Bioinformatics Analysis

Xingshu ZHU¹(), Junjie HUANG¹, Caiming WENG², Wangwu LIU², Yongyuan CHEN², Huiyan CHEN², Hu ZHAO²^,³, Yu WANG²^,³, Chengzhi LIN²^,³()

^1.College of Integrated Medicine，Fujian University of Traditional Chinese Medicine，Fuzhou 350122，China
^2.Fuzhou General Clinical Medical College of Fujian Medical University （900TH Hospital），Fuzhou 350025，China
^3.900TH Hospital of Joint Logistics Support Force，Fuzhou 350025，China

Received:2022-07-01 Accepted:2022-08-18 Online:2023-03-25 Published:2023-04-07
Contact: Chengzhi LIN

摘要/Abstract

摘要：

通过生物信息学方法筛选出与林奇综合征相关结直肠癌（colorectal cance，CRC）组织中的差异表达基因（differentially expressed genes，DEGs）。从基因表达总库（gene expression omnibus，GEO）下载林奇综合征相关CRC数据集GSE178516，使用GEO2R筛选DEGs，并在人类疾病数据库Malacards中获取CRC和林奇综合征疾病基因，3者的交集取为关键Hub基因，通过功能富集分析鉴定DEGs。利用String数据库构建蛋白质-蛋白质相互作用网络（protein-protein interaction，PPI），并使用Cytoscape软件对PPI网络进行可视化和模块分析。随后在easyGEO数据库中对差异表达基因进行表达验证。从GSE178516共鉴定出261个差异基因，包括117个上调基因和114个下调基因。这些基因与CRC和林奇综合征基因共交集出8个差异表达基因（TGFBR2、PTEN、POLD1、EXO1、EPCAM、CDKN2B、CCND1、BRCA1）。GO、KEGG富集分析显示，其功能主要富集在DNA代谢过程调控、内在凋亡信号通路、错配修复等方面；KEGG通路分析主要富集在CRC等相关癌症路径。通过PPI获得与67个差异表达蛋白存在相互作用关系的892个蛋白，并利用Cytoscape软件构建其重要模块，包含44个节点和630个节点作用关系。利用easyGEO网站对8个差异基因进行表达分析，发现8个基因在林奇综合征相关CRC患者中的表达均具有统计学差异。总体上，研究鉴定出的关键Hub基因有助于了解林奇综合征相关CRC发生和发展的分子机制，并为林奇综合征进展对CRC的诊断和治疗提供新的候选靶点。

关键词: 林奇综合征, 结直肠癌, 差异表达基因, Hub基因, 生物信息学

Abstract:

To screen the differentially expressed genes （DEGs） in Lynch syndrome related colorectal cancer （CRC） by various bioinformatic analysis. The dataset GSE178516 was downloaded from gene expression omnibus （GEO）. DEGs were screened by employing the GEO2R tool， and then intersected with the genes related to CRC and Lynch syndrome from the MalaCards to obtain the common differential genes. Then the functional enrichment analysis and protein-protein interaction （PPI） network was constructed by using String and Cytoscape software. Finally， expressions of the hub genes were verified by easyGEO database. A total of 261 differentially expressed genes were identified， consisting of 117 up-regulated genes and 114 down-regulated genes. After intersection with CRC and Lynch syndrome related genes， a total of 8 genes （TGFBR2， PTEN， POLD1， EXO1， EPCAM， CDKN2B， CCND1， BRCA1） were obtained. GO and KEGG enrichment analysis showed that their functions were mainly enriched in DNA metabolic process regulation， intrinsic apoptosis signaling pathway， mismatch repair， etc. Through PPI analysis， 892 proteins interacting with 8 common DEGs were obtained， including 44 nodes and 630 node interaction relationships. Finally， all 8 genes were statistically differentially expressed in patients with CRC associated with Lynch syndrome. The key Hub genes identified in this study would help us understand the molecular mechanisms behind the occurrence and development of Lynch syndrome combined with CRC， and ultimately provide new candidate targets for the diagnosis and treatment of Lynch syndrome progression to CRC.

Key words: Lynch syndrome, colorectal cancer, differentially expressed gene, Hub gene, bioinformatics

中图分类号:

Q811.4

朱兴墅, 黄军杰, 翁才明, 刘旺武, 陈永元, 陈惠燕, 赵虎, 王瑜, 林承志. 基于生物信息学分析林奇综合征相关结直肠癌关键Hub基因的筛选与功能富集分析[J]. 生物技术进展, 2023, 13(2): 291-297.

Xingshu ZHU, Junjie HUANG, Caiming WENG, Wangwu LIU, Yongyuan CHEN, Huiyan CHEN, Hu ZHAO, Yu WANG, Chengzhi LIN. Screening and Functional Enrichment Analysis of Key Hub Genes in Lynch Syndrome-associated Colorectal Cancer Based on Bioinformatics Analysis[J]. Current Biotechnology, 2023, 13(2): 291-297.

图/表 4

图1 DEGs的筛选A：GSE178516数据集通过GEO2R分析后，以校正P<0.05且绝对值|logFC|≥1为筛选标准构建差异基因火山图；B：林奇综合征相关CRC的癌旁样本和肿瘤样本基因聚类结果显示，两组间存在基因的显著差异表达；C：林奇综合征及结直肠癌疾病基因和GSE178516 DEGs交集的Venn图

Fig. 1 Screening of DEGs

图2 差异基因功能富集分析A：将交集出的69种DEGs进行 GO、KEGG分析，明确DEGs的主要富集通路；B：基于功能富集结果构建GO|KEGG 网络

Fig. 2 Functional enrichment analysis of differential genes

图3 PPI网络构建和模块分析A：通过String数据库构建DEGs的PPI网络；B：通过Cytoscape中的MCODE插件提取PPI网络中最重要的模块

Fig. 3 PPI network construction and module analysis

图4 GSE178516数据集中关键Hub基因的表达分析A~D：GSE178516数据集中CCND1、BRCA1、POLD1、EXO1基因在林奇综合征相关CRC的肿瘤组织中高表达；E~H：GSE178516数据集中PTEN、EPCAM、CDKN2B、TGFBR2基因在林奇综合征相关CRC的肿瘤组织中低表达

Fig. 4 Expression analysis of Hub genes in GSE178516

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基于生物信息学分析林奇综合征相关结直肠癌关键Hub基因的筛选与功能富集分析

Screening and Functional Enrichment Analysis of Key Hub Genes in Lynch Syndrome-associated Colorectal Cancer Based on Bioinformatics Analysis

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