应用肿瘤数据库信息分析HMCN1基因在胃腺癌中的表达及其作用机制

Application of tumor database information to analyze the expression and its potential mechanism of HMCN1 gene in gastric adenocarcinoma

目的:通过对癌症基因图谱(the Cancer Genome Atlas,TCGA)等相关数据库的信息挖掘,研究HMCN1基因在胃腺癌中的表达,探讨其与胃腺癌发生发展的潜在机制。方法:获得Cbioportal在线分析TCCGA数据库中289例胃腺癌患者的RNA数据,结合患者的生存时间信息,应用Kaplan-Meier法分析HMCN1变异与胃腺癌患者生存之间的关系。利用基因表达谱动态分析(GEPIA)数据库信息,搜索HMCN1 mRNA在正常胃腺组织与胃腺癌组织表达的区别,分析其在不同病理分期中的表达情况。应用Genecards数据库收集与HMCN1基因的相关蛋白,绘制HMCN1相关蛋白网络图,对相关蛋白进行富集分析,分析蛋白富集的信号通路、生理过程及关键下游蛋白。结果:289例胃腺癌中有66例(23%)发生HMCN1基因突变,HMCN1变异组总生存时间长于无变异组(P=0.015 3),变异组无病生存时间与无变异组生存时间差异无统计学意义(P=0.052 3)。胃腺癌组织中HMCN1 mRNA表达明显高于正常胃腺组织;与HMCN1相关的蛋白有CTDSPL、DDX1、CLP1、CFB等25个,其中CTDSPL蛋白在胃腺癌中表达降低,相关蛋白富集分析得到Wnt信号通路、Hippo信号通路、丝氨酸型内肽酶活性通路等细胞组织生理活动。结论:胃腺癌组织中HMCN1 mRNA呈高表达,其可能通过促进CTDSPL蛋白降解发挥抑癌基因的作用。

Objective： To study the expression of the HMCN1 gene in gastric adenocarcinoma, and its potential mechanism in the development of gastric adenocarcinoma, through mining the information of the Cancer Genome Atlas（TCGA） and other related databases. Methods： The RNA data of 289 patients with gastric adenocarcinoma in TCGA database were analyzed online by Cbioportal. With the patient＇s survival time information, Kaplan-Meier Curve was used to analyze the relationship between the HMCN1 variation and the survival of the patients with gastric adenocarcinoma. The information of GEPIA database was used to search for the difference in HMCN1 expression between normal tissues and tumor tissues, and explore their expression in different pathological stages. The Genecards database was used to collect the related protein of HMCN1 gene and the network diagram of HMCN1 related protein was drawn. The related proteins were enriched and analysed the signal pathway, physiological process and the key downstream proteins. Results ： In 289 cases of gastric adenocarcinoma, 66 cases（23%） had HMCNI gene mutation;the total survival time of the HMCN1 variant group was longer than that of the non-variant group（P =0.015 3）, but there was no significant difference in the disease-free survival time between the variant group and the non-variant group（P = 0. 052 3）. There were 25 proteins related to HMCN1, such as CTDSPL, DDX1, CLP1 and CFB, among which the expression of CTDSPL protein was reduced in gastric adenocarcinoma,and the accumulation and analysis of related proteins might be involved in the cellular tissue and physiological activities of Wnt signaling pathway, Hippo signaling pathway, serine type endopeptidase activity and so on. Conclusion ： HMCN1 was highly expressed in gastric adenocarcinoma tissues, which might play a role in tumor suppressor gene by promoting CTDSPL protein degradation.