ATP6V1C2在结肠癌中的表达及其临床意义

Expression and clinical significance of ATP6V1C2 in colon cancer

目的:筛选结肠癌(CC)中差异性表达的自噬相关基因(ATGs),并分析其临床意义。方法:从HADb和MSigDB数据库收集ATGs,并联合TCGA数据库(结肠癌患者)的mRNA数据及临床信息,采用R软件筛选出差异表达的ATGs,并对其进行GO功能分析及KEGG通路富集分析。单因素及多因素Cox回归模型分析预后相关的ATGs,构建患者预后指数评分模型(PIS)鉴定影响患者预后的关键基因。绘制生存曲线(KM)验证关键基因对结肠癌患者预后的作用,验证关键基因与临床参数的相关性,并通过qRT-PCR证实关键基因在组织标本中的表达差异。结果:从获得的601个ATGs中筛选出85个差异性表达的ATGs(DEARGs),提示与自噬密切相关(FDR<0.05,|log2FC|>1)。Cox回归模型筛选出4个与患者预后相关的ATGs(ATP6V1B1、UCHL1、ATP6V1C2、TUBA4B)。PIS预后模型鉴定ATP6V1C2为关键基因(P=0.02)。KM生存曲线揭示ATP6V1C2高表达与结肠癌患者的不良预后成正比(P=0.0027)。TCGA结肠癌患者临床分期越晚、淋巴结转移程度越高、有远处转移发生,ATP6V1C2的表达水平越高(P<0.05)。ATP6V1C2在结肠癌肿瘤组织中表达水平显著高于正常癌旁组织(P<0.01)。结论:ATP6V1C2或可成为结肠癌患者预后的有效监测指标。

Objective:Autophagy-related Genes(ATGs)differentially expressed in colon cancer(CC)were screened and their clinical significance was analyzed.Methods:ATGs were collected from HADB and MSIGDB databases,combined with mRNA data and clinical information from the TCGA database(colon cancer patients).Differentially expressed ATGs were screened by R software,and the GO function analysis and KEGG pathway enrichment analysis were performed.Univariate and multivariate Cox regression models were used to analyze theprognostic ATGs and constructed the Prognostic Index Score(PIS)to identify hub genes associated with patient outcomes.The survival curve(Kaplan-Meier,KM)was drawn to confirm the influence of hub gene on the prognosis of patients with colon cancer,t-test verified the correlation between hub genes and clinical parameters,and qRT-PCR affirmed the expression differences of hub genes in tissue samples.Results:A total of 85 difference expression ATGs(differential expression autophagy-related genes,DEARGs)were extracted from the 601 ATGs,which was closely related to the autophagy(FDR<0.05,|log2FC|>1).Four ATGs(ATP6V1B1,UCHL1,ATP6V1C2,and TUBA4B)were screened by the Cox regression model.PIS prognostic model identified ATP6V1C2 as the hub gene(P=0.02).KM survival curve revealed that the high expression of ATP6V1C2was positively correlated with poor prognosis in colon cancer patients(P=0.0027).T-test and the rank-sum test confirmed that the later clinical stage,the higher degree of lymph node metastasis and distant metastasis of TCGA colon cancer patients,the higher the expression level of ATP6V1C2 was(P<0.05).The expression level of ATP6V1C2 in colon cancer tissues was significantly higher than that in normal paracancerous tissues(P<0.01).Conclusion:ATP6V1C2 may be an effective indicator of prognosis in patients with colon cancer.