TCGA数据库分析EGFR在结直肠癌中的分子特征、致癌作用以及相关免疫和药物基因组学特征  

TCGA database analysis of EGFR molecular characteristics carcinogenic role and related immune pharmacogenomic features in colorectal cancer

作　　者：金雷 唐晓磊 顾俊菲 Jin Lei;Tang Xiaolei;Gu Junfei(Gastroenterology Department,the Second Affiliated Hospital of Wannan Medical College,Wuhu,Anhui 241000,China;Translational Medicine Center,the Second Affiliated Hospital of Wannan Medical College,Wuhu,Anhui 241000,China;Endocrinology Department,the Second Affiliated Hospital of Wannan Medical College,Wuhu,Anhui 241000,China)

机构地区：[1]皖南医学院第二附属医院消化内科,安徽芜湖241000 [2]皖南医学院第二附属医院转化医学中心,安徽芜湖241000 [3]皖南医学院第二附属医院内分泌科,安徽芜湖241000

出　　处：《齐齐哈尔医学院学报》2024年第17期1606-1614,共9页Journal of Qiqihar Medical University

基　　金：安徽省自然青年基金项目(2308085QH260);芜湖市科技计划重点研发项目(2023jc24);芜湖市卫生健康委员会科研项目(WHWJ2023y013)。

摘　　要：目的 探讨EGFR在结直肠癌中的分子表达与结肠癌增殖转移,肿瘤免疫和肿瘤信号通路以及肿瘤预后中的作用。方法 从TCGA数据库下载结直肠癌的mRNA表达数据和癌旁组织及对应的临床资料数据,使用在线网站TIMER2.0分析泛癌中EGFR的表达情况;使用Deseq2程序包分别对miRNA和mRNA的表达数据进行差异基因筛选,采用Spearman相关性分析,探讨EGFR与上述因素在泛癌中的相关性;单样本基因集富集分析(single sample gene set enrichment analysis, ssGSEA)推断肿瘤浸润免疫细胞的丰度;用pRRophetic包估计代表药物反应的半抑制浓度(IC50)进行癌症药物敏感性评估;使用miRWalk预测EGFR靶向的miRNA并通过miRmap预测结合位点。结果 EGFR与相应的正常样本相比,在大多数癌症类型中表达呈现降低的趋势,包括结直肠癌;在结直肠癌中,EGFR表达与DNA甲基转移酶、DNA错配修复基因、m6A调节因子、TMB和MSI显著相关。EGFR高表达提示结直肠癌患者预后不良。此外,其表达上调与免疫细胞浸润增强、基质和免疫激活增加、肿瘤免疫周期活性升高有关。在EGFR高表达亚群中研究了更高频率的扩增和缺失。经验证,EGFR衍生的基因组模型可靠地预测了患者的预后和药物反应。高EGFR表达亚群中,体细胞更容易发生突变;通过GSEA涉及EGFR的信号通路发现,EGFR参与了多种致癌途径,表明了EGFR的致癌作用;EGFR衍生基因可能在结直肠癌进展中发挥显著作用。结论 本研究结果为指导EGFR在结直肠癌中的作用机制和治疗分析提供了有价值的线索。Objective To investigate the molecular expression of EGFR in colorectal cancer and its role in colon cancer proliferation and metastasis,tumor immunity and tumor signaling pathways,and tumor prognosis.Methods The mRNA expression data of colorectal cancer were downloaded from the TCGA database,as well as the adjacent tissues and corresponding clinical data.The online website TIMER2.0 was used to analyze the expression of EGFR in pancancer.The Deseq2 program package was used to screen the differential genes of miRNA and mRNA expression data.Spearman correlation analysis was used to explore the correlation between EGFR and the above factors in pancancer.The abundance of tumor infiltrating immune cells was deduced by single sample gene set enrichment analysis(ssGSEA).The half maximum inhibitory concentration(IC50)that representing the drug reaction was estimated by pRRophic package,and it was used to evaluate the sensitivity of cancer drugs.miRWalk was used to predict the EGFR targeted miRNA and predict the binding site through miRmap.Results Compared with the corresponding normal samples,the expression of EGFR showed a downward trend in most cancer types,including colorectal cancer.In colorectal cancer,the expression of EGFR was significantly correlated with DNA methyltransferase,DNA mismatch repair gene,m6A regulator,TMB and MSI.The high expression of EGFR suggested poor prognosis in patients with colorectal cancer.In addition,the up-regulation of its expression was related to the increased infiltration of immune cells,the increase of matrix and immune activation,and the increase of tumor immune cycle activity.A higher frequency of amplification and deletion was studied in the high expression subgroup of EGFR.It had been proved that the genome model derived from EGFR could reliably predict the prognosis and drug response of patients.Somatic cells were more prone to mutation in high EGFR expression subgroups.Through the signal pathway of GSEA involving EGFR,it was found that EGFR participated in many carcinogenic pa

关 键 词：结直肠癌 EGFR 预后 肿瘤免疫 药物基因组学特征 

分 类 号：R574.1[医药卫生—消化系统]