自噬基因结肠癌预后模型建立及验证  

Establishment and validation of prognosis model of autophagy gene in colon cancer

作　　者：王竣立 陶成成 乔玲 游江舟 李昌龙[1] WANG Junli;TAO Chengcheng;QIAO Ling;YOU Jiangzhou;LI Changlong(West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China)

机构地区：[1]四川大学华西基础医学与法医学院生物化学教研室,四川成都610041

出　　处：《西部医学》2021年第2期173-179,共7页Medical Journal of West China

基　　金：四川省科技计划项目(2019YJ0050)。

摘　　要：目的通过筛选结肠癌预后自噬相关基因,构建一种基于差异表达自噬基因的结肠癌预后模型,探讨其特征及临床意义。方法在癌症基因组数据库(TCGA)中,检索结肠癌的转录组数据,利用wilcox检验进行差异分析,筛选出结肠癌差异表达的自噬基因,对其进行KEGG pathway和GO功能富集分析。结合临床信息,使用COX分析筛选出结肠癌预后相关差异表达的自噬基因,构建预后风险预测模型并进行单因素及多因素回归分析验证。结果共收集524例样本,其中42例正常样本,482例结肠癌肿瘤样本;发现结肠癌差异表达自噬基因35个,其中16个基因上调,19个基因下调;GO与KEGG富集分析结果显示:差异表达的自噬基因主要分布在自噬、凋亡、氧化应激、细胞色素c释放以及肿瘤耐药方面。结合患者临床信息,本研究对差异表达自噬基因进行COX分析,共筛选出5个差异表达自噬基因WIPI2、RAB7A、ULK3、PELP1和DAPK1参与构建风险计算模型。生存曲线和风险曲线显示:本模型与患者生存率存在显著相关性,且预后模型、参与模型构建的基因与癌症分期、病人年龄均存在统计学意义。通过Real-time PCR实验检测对本模型风险值贡献最大的RAB7A基因及WIPI2基因在人正常结肠细胞(NCM460)与人结肠癌细胞(HCT116、RKO)中的表达水平,结果显示在人结肠癌细胞中RAB7A及WIPI2基因表达水平高于人正常结肠细胞(P<0.05)。结论通过COX回归分析成功地构建出基于差异表达自噬基因的结肠癌预后模型,该模型筛选的结肠癌预后自噬相关基因可作为结肠癌预后独立危险因子。Objective To construct a prognostic model of colon cancer based on differential expression of autophagy genes and explore its characteristics and clinical significance.Methods In the cancer genome database(TCGA),the transcriptome data of colon cancer were retrieved.Wilcox test was used for differential analysis to screen out the differentially expressed autophagy genes of colon cancer,and KEGG pathway and GO function enrichment analysis were performed.Combined with clinical information,Cox analysis was used to screen out the differentially expressed autophagy genes related to the prognosis of colon cancer,and the prognostic risk prediction model was constructed and verified by univariate and multivariate regression analysis.Results 524 samples were collected,including 42 normal samples and 482 tumor samples.35 autophagy differentially expression genes were detected,among which 16 were up-regulated and 19 were down-regulated.The results of GO and KEGG enrichment analysis showed that the main functions of the differential genes were autophagy,apoptosis,oxidative stress,cytochrome c release and anti-tumor drug resistance.Univariate COX analysis was conducted and 10 prognostic related autophagy genes were defined.After multi-factor COX analysis,a total of 5 genes(WIPI2,RAB7A,ULK3,PELP1 and DAPK1)were screened to participate in the construction of risk calculation model.Survival curve and risk curve showed that this prognosis model was significantly correlated with patient survival.Analysis with clinical information indicates that the prognostic model and the autophagy genes involved in the model construction were significantly correlated with tumor stage and age.Real-time PCR was performed to detect the expression levels of RAB7A gene and WIPI2 gene,which contributed the most to the risk value of this model,in normal human colon cells(NCM460)and human colon cancer cells(HCT116 and RKO).The results showed that the expression levels of RAB7A gene and WIPI2 gene in human colon cancer cells were higher than that in norma

关 键 词：结肠癌 自噬基因 预后模型 COX回归分析 独立危险因子 

分 类 号：R735.3+5[医药卫生—肿瘤]