通过共表达分析抑制素βA基因表达与肠正常黏膜到腺瘤再到腺癌进展的关系  

The correlation between inhibinβA gene expression and the progression from normal mucosa to adenoma to adenocarcinoma was analyzed by co-expression analysis

作　　者：孙萌 郑新宇 陈志芬[3] 刘小平[4] 姜毅楠 张姮[1] 李炫飞 Sun Meng;Zheng Xinyu;Chen Zhifen;Liu Xiaoping;Jiang Yinan;Zhang Heng;Li Xuanfei(Department of Gastroenterology,the Central Hospital of Wuhan,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430014,China;Department of Gastrointestinal Surgery,Zhongnan Hospital of Wuhan University,Clinical Medical Research Center of Peritoneal cancer of Wuhan,Clinical Cancer Study Center of Hubei Province,Key Laboratory of Tumor Biological Behavior of Hubei Province,Wuhan 430071,China;Department of Gastroenterology,Zhongnan Hospital of Wuhan University,Hubei Clinical Center and Key Laboratory for Intestinal and Colorectal Diseases,Wuhan 430071,China;Department of Pathology,Zhongnan Hospital of Wuhan University,Wuhan 430071,China)

机构地区：[1]华中科技大学同济医学院附属武汉中心医院消化内科,430014 [2]武汉大学中南医院胃肠外科武汉市腹膜癌临床医学研究中心湖北省肿瘤医学临床研究中心肿瘤生物学行为湖北省重点实验室,430071 [3]武汉大学中南医院消化内科湖北省肠病重点实验室肠病湖北省临床研究中心,430071 [4]武汉大学中南医院病理科,430071

出　　处：《中华实验外科杂志》2022年第10期1987-1990,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金(82070302,1902018);湖北省卫生健康委员会面上项目(WJ2021M167);武汉大学中南医院科技创新培育基金资助项目(CXPY2022055)。

摘　　要：目的寻找与肠正常黏膜(NOR)到结直肠腺瘤(CRA)再到结直肠癌(CRC)的进展密切相关的基因。方法利用数据集GSE37364(包括38例NOR,29例CRA及27例CRC)构建加权基因共表达网络分析(WGCNA),选择软阈值为10确保基因无尺度网络分布,构建关系矩阵转换为邻接矩阵,进一步构建拓扑重叠矩阵鉴定与疾病进展相关的基因模块并寻找其枢纽(Hub)基因。对Hub基因在数据集GSE20916中进行单因素方差分析及组间t检验,数据集GSE14333中进行t检验,以确认Hub基因与疾病进展的相关性。结果筛选出1858个差异表达基因进行分析,确定一个重要的基因模块(黄色模块)和该模块中的4个Hub基因:抑制素βA(INHBA)、趋化因子配体8(CXCL8)、趋化因子配体1(CXCL1)、CCAAT增强子结合蛋白(CEBPB),进一步线性回归分析发现INHBA与疾病进展高度相关(R^(2)=0.793)。基因富集分析表明,该模块中的INHBA主要参与细胞增殖的调控。在GSE20916数据集中进行分析,INHBA在NOR、CRA、CRC中表达分别为2.732±0.1441、2.81±0.1347、2.946±0.1603,INHBA表达与NOR至CRA再至CRC的进展密切相关(F=16.99,P<0.0001),在CRA及CRC表达均高于NOR(P<0.05),在CRC中表达高于CRA中表达(P<0.01)。在数据集GSE14333中,INHBA表达在Dukes分期A、B、C、D期CRC中表达分别为9.658±1.349、10.32±1.105、10.56±1.234、10.26±1.26,Dukes分期B、C、D中INHBA表达均高于Dukes分期A期CRC,差异有统计学意义(P<0.05),在B、C、D期中表达差异无统计学意义。结论通过共表达分析发现INHBA可能通过调节细胞增殖与NOR、CRA和CRC的进展有关。Objective To explore genes that had strong correlations with the progression from normal colonic mucosa(NOR)to colorectal adenoma(CRA)and then to colorectal cancer(CRC).Methods In dataset GSE37364(including 38 NOR samples,29 CRA samples and 27 CRC samples),a weighted gene co-expression network was constructed to identify gene modules and their hub genes associated with the disease progression.A soft threshold of 10 was chosen to ensure that genes were distributed in a scale-free network,and a relationship matrix was constructed to convert it into an adjacency matrix,and a topological overlap matrix was further constructed to identify gene modules related to disease progression and search for their hub genes.One-way ANOVA and t-test were performed on Hub gene in dataset GSE20916,and t-test was performed in dataset GSE14333 to confirm the correlation between Hub gene and disease progression.Results A total of 1858 DEGs were selected for subsequent analysis.One significant module(yellow)and a total of 4 hub genes(INHBA,CXCL8,CXCL1,CEBPB)were identified.In further analysis,only INHBA showed a high correlation with the disease progression(R^(2)=0.793).Gene Ontology analysis showed INHBA was mainly involved in regulation of cell proliferation.In the GSE20916 dataset,the expression of INHBA in NOR,CRA,and CRC was 2.732±0.1441,2.81±0.1347,2.946±0.1603.The expression of INHBA was closely related to the progression from NOR to CRA and then to CRC(F=16.99,P<0.01).The expression of INHBA was higher in CRA and CRC than in NOR(P<0.05),and higher in CRC than in CRA(P<0.01).In dataset GSE14333,INHBA expression was 9.658±1.349,10.32±1.105,10.56±1.234,10.26±1.26 in Dukes stage A,B,C,and D CRC,respectively.The expression of INHBA in Dukes stage B,C and D was higher than that in Dukes stage A,and the difference was statistically significant(P<0.05).The expression of INHBA in stage B,C and D has no statistical significance.Conclusion Through co-expression analysis,INHBA was identified and validated to be associated with the pr

关 键 词：结直肠癌 抑制素βA 共表达分析 加权基因共表达网络分析 

分 类 号：R735.34[医药卫生—肿瘤]