基于TCGA和GEO数据挖掘分析NAT1在结肠癌中的表达及预后意义  

The expression and prognosis value of N-acetyltransferase 1 in colon cancer:a study based on TCGA and GEO Database

作　　者：陈俊杰[1] 郭浩然 施波 陈国梁 邰清亮 侍新宇 姚慧慧 米秀伟 王索 孙金兵 周迪远 顾闻[1] 何宋兵[1] Chen Junjie;Guo Haoran;Shi Bo;Chen Guoliang;Tai Qingliang;Shi Xinyu;Yao Huihui;Mi Xiuwei;Wang Suo;Sun Jinbing;Zhou diyuan;Gu Wen;He Songbing(Department of General Surgery,First Affiliated Hospital of Soochow University,Suzhou 215000,China;Department of Biochemistry and Molecular Biology,Soochow University Medical College,Suzhou 215000,China;Department of General Surgery,Changshu No.1 People's Hospital,Affiliated Changshu Hospital of Soochow University,Suzhou 215500,China)

机构地区：[1]苏州大学附属第一医院普外科,215000 [2]苏州大学基础医学院生物化学与分子生物学系,215000 [3]常熟市第一人民医院普外科,215500

出　　处：《中华结直肠疾病电子杂志》2022年第5期399-408,共10页Chinese Journal of Colorectal Diseases(Electronic Edition)

基　　金：江苏省自然科学基金(No.BK20191172);苏州市医工结合协同创新研究项目(No.SLJ2021007);苏州市姑苏卫生重点人才项目(No.GSWS2020005);苏州市科技局科研项目(No.SYS2020058);常熟市D类“临床医学专家团队”引进项目(No.CSYJTD202101)。

摘　　要：目的探讨结肠癌癌组织中N-乙酰化转移酶1(NAT1)的表达及其对结肠癌患者预后的影响。方法通过肿瘤免疫评估资源(TIMER)数据库分析NAT1 mRNA在33种肿瘤中的表达情况,并用人类蛋白质图谱(HPA)数据库的免疫组化结果验证NAT1蛋白在结肠癌中的表达。通过肿瘤基因图谱(TCGA)和基因表达综合(GEO)数据库获得NAT1在结肠癌中的表达数据及相关临床特征参数,分析NAT1 mRNA表达水平与结肠癌患者的临床特征和总生存期(OS)的关系,并构建预后模型。采用基因集富集分析(GSEA)预测NAT1相关的基因通路。采用CIBERSORT分析NAT1与免疫浸润的关系。结果TIMER数据库分析结果显示,在13种肿瘤组织中NAT1 mRNA表达水平低于正常对照组织。TCGA数据库结果提示,结肠癌组织中NAT1 mRNA表达水平均明显低于正常对照组织或癌旁正常组织,差异均有统计学意义(均P<0.01),并在GSE44076、GSE44861和GSE73360中得到验证。HPA数据库的免疫组化结果提示,NAT1蛋白在结肠癌组织中呈低表达。TCGA数据库分析结果提示,NAT1 mRNA表达水平与结肠癌患者的N分期、M分期和stage分期均有关(均P<0.01)。NAT1高表达组患者OS均好于低表达组(均P<0.05)。单因素Cox分析表明,NAT1 mRNA表达水平是影响结肠癌患者OS的危险因素(P<0.05),并和其他危险因素构建列线图,同时使用校准曲线和ROC评估了预后模型的特异性和敏感性。选取本院确诊的35例结肠癌患者肿瘤组织作为肿瘤组,选取其癌旁正常组织作为对照组。采用实时荧光定量PCR(qRT-PCR)法检测NAT1表达水平,结果与数据库结果一致(P<0.05)。GSEA结果提示NAT1高表达样本上调抗坏血酸和醛糖酸盐代谢、戊糖和葡萄糖醛酸的相互转化、淀粉和蔗糖代谢、卟啉和叶绿素代谢途径、视黄醇代谢、药物代谢相关酶等基因集,而下调糖胺聚糖生物合成途径、Hedgehog信号通路、基底细胞癌、ECM受体作用通路、神�Objective To investigate the expression of N-acetyltransferase 1(NAT1)in colon cancer(CC)and its relation with prognosis of patients.Methods The expression of NAT1 mRNA in 33 tumors was analyzed based on TIMER database,and immunohistochemical method was used to verify the expression of NAT1 protein in CC using HPA database.The correlation between NAT1 mRNA expression and CC clinical pathology parameters overall survival(OS)was studied using TCGA and GEO databases.GSEA was applied to predict the potential signaling pathways.The CIBERSORT algorithm was used to investigate the correlation between the immune cells and NAT1.Results The TIMER database showed that NAT1 mRNA expression was significantly down-regulated in 13 tumors.Based on TCGA database,GSE44076、GSE44861 and GSE73360,the expression level of NAT1 in CC tissues was significantly lower than that of normal tissues and adjacent normal tissues(all P<0.01).The immunohistochemical results of the HPA database suggested that NAT1 protein was lowly expressed in CC tissues.The TCGA database showed that NAT1 mRNA expression was significantly correlated with,N stage,M stage and TNM tumor stage(all P<0.05).the OS of patients with high expression of NAT1 were significantly better than those of patients with low expression(all P<0.05).Univariate and multivariate Cox analysis showed that NAT1 was risk factor affecting OS of CC patients and the nomogram was constructed.Tumor tissues of 35 patients with colon cancer were selected as the colon cancer group,and the adjacent normal tissues were selected as the control group.Real-time fluorescence quantitative PCR(qRT-PCR)was used to detect the expression level of NAT1,which is consistent with predictions.GSEA showed that the high expressions of NAT1 up-regulated ascorbate and aldarate metabolism,pentose and glucuronate interconversions,starch and sucrose metabolism,porphyrin and chlorophyll metabolism,retinol metabolism,drug metabolism-other enzymes;while down-regulated glycosaminoglycan biosynthesis pathway,hedgehog signali

关 键 词：结肠肿瘤 N-乙酰化转移酶1 肿瘤基因图谱数据库 基因表达综合数据库 预后 

分 类 号：R735.35[医药卫生—肿瘤]