摘要
目的基于生物信息学探讨结肠腺癌中胶原三股螺旋重复蛋白1(CTHRC1)基因表达的意义。方法采用GEPIA2分析工具分析癌症基因组图谱(TCGA)数据库和GTEx数据库中结肠腺癌CTHRC1基因的表达及其与患者生存预后之间的关系;采用ULACAN分析工具分析TCGA数据库中CTHRC1基因在结肠腺癌组织和正常结肠组织中的甲基化水平。采用cBioportal网络分析工具分析CTHRC1基因突变。采用TIMER分析工具分析基因表达与免疫细胞浸润、肿瘤相关成纤维细胞浸润以及功能性免疫细胞之间的关系。采用STRING数据库分析与CTHRC1相互作用的蛋白,并进行富集分析。结果在结肠腺癌组织中,CTHRC1基因和蛋白的表达水平均高于正常结肠组织,差异均有统计学意义(均P<0.01),且CTHRC1基因在正常结肠组织中呈现高甲基化水平,在肿瘤组织中为低甲基化水平(P<0.01)。2480份结直肠腺癌和结肠腺癌样本中共检出19例突变,其中结肠腺癌标本CTHRC1突变3例,突变位点为R235H、A124V和R193C,突变类型均为错义突变。CTHRC1基因表达与CD8^(+)T细胞、CD4^(+)T细胞、巨噬细胞、中性粒细胞、树突细胞、肿瘤相关成纤维细胞浸润均呈正相关(均P<0.01)。CTHRC1基因高表达患者的总生存、无病生存均差于CTHRC1基因低表达患者(均P<0.05)。结论CTHRC1基因甲基化、肿瘤相关免疫细胞的浸润可能在结肠腺癌的发病过程中具有重要意义,CTHRC1基因表达和免疫细胞浸润可以作为结肠腺癌患者生存预后的预测指标。
Objective To investigate the significance of collagen triple helix repeat containing 1(CTHRC1)gene expression in colon adenocarcinoma based on bioinformatics.Methods The GEPIA2 analysis tool was used to analyze the expression of CTHRC1 gene in colon adenocarcinoma and the relationship between its expression and the survival prognosis of patients in The Cancer Genome Atlas(TCGA)database and GTEx database.ULACAN analysis tool was used to analyze the methylation level of CTHRC1 gene in colon adenocarcinoma tissues and normal colon tissues in TCGA database.The cBioportal network analysis tool was used to analyze the mutation of CTHRC1 gene.TIMER analysis tool was used to analyze the relationship between CTHRC1 expression and immune cells infiltration,tumor⁃associated fibroblasts infiltration and functional immune cells.STRING database was used to analyze the proteins interacted with CTHRC1,and the enrichment analyses were performed.Results The expressions of CTHRC1 gene and protein in colon adenocarcinoma tumor tissues were higher than those in normal colon tissues,and the differences were statistically significant(both P<0.05),and CTHRC1 gene showed high methylation level in normal colon tissues and low methylation level in tumor tissues(P<0.05).A total of 19 mutations were detected in 2480 colorectal adenocarcinoma and colon adenocarcinoma samples.Among them,3 cases of colon adenocarcinoma specimens had CTHRC1 mutations,the mutation sites were R235H,A124V and R193C,and the mutation types were all missense mutations.CTHRC1 gene expression was positively correlated with infiltrations of CD8^(+)T cells,CD4^(+)T cells,macrophages,neutrophils,dendritic cells and tumor⁃associated fibroblasts(all P<0.01).The overall survival and disease⁃free survival of patients with high expression of CTHRC1 gene were worse than those of patients with low expression of CTHRC1 gene(all P<0.05).Conclusions The methylation of CTHRC1 gene and the infiltration of tumor⁃associated immune cells may have important significances in the pa
作者
杨丰美
高波
Yang Fengmei;Gao Bo(Department of Obstetrics and Gynecology,Taihe Hospital of Shiyan City in Hubei Province,Shiyan 442000,China;Department of Laboratory Medicine,Taihe Hospital of Shiyan City in Hubei Province,Shiyan 442000,China)
出处
《肿瘤研究与临床》
CAS
2021年第11期824-829,共6页
Cancer Research and Clinic
基金
湖北省自然科学基金(2016CFB154)
十堰市科学技术研究与开发项目(18Y27)。
关键词
结肠肿瘤
腺癌
计算生物学
胶原三股螺旋重复蛋白1
Colonic neoplasms
Adenocarcinoma
Computational biology
Collagen triple helix repeat containing 1
