LncRNA与肝细胞癌关联TCGA数据库信息分析评价

LncRNA and hepatocellular carcinoma prognosis:A bioinformatic analysis base on TCGA database

目的肝细胞癌是常见的恶性肿瘤,而lncRNA与肝细胞癌的发生、发展有关联,目前基于癌症和肿瘤基因图谱(Cancer Genome Atlas,TCGA)的肝癌lncRNA预后模型仍有待研究。本研究旨在探索肝癌预后有关联的lncRNA,构建肝癌lncRNA预后模型。方法从TCGA公共数据库下载肝癌的lncRNA表达谱和临床信息,筛选出肝癌组织和癌旁对照组织表达差异有统计学意义的基因。结合生存信息,筛选预后关联的基因。最后利用LASSO回归构建预后模型并验证。结果共筛选出1292个在癌与癌旁组织中差异表达lncRNA,其中142个与预后有关联,P<0.05。LASSO回归模型包含9个lncRNA,分别为AC010547.1、AC034229.4、AL121721.1、AP003390.1、BBOX1-AS1、LINC00462、LINC00942、LINC01353和LINC01954。此lncRNA模型可以很好地预测肝癌患者的生存,多因素Cox回归结果模型风险比为2.60(95%CI:2.18~3.21),Log-rank检验P=1.72e-6。结论lncRNA模型可良好地预测肝癌患者生存,处于模型中的lncRNA也进一步为治疗靶点及预后分子标志物的选择提供了依据。

OBJECTIVE Hepatocellular carcinoma(HCC)is a common type of malignant tumor,while lncRNAs are closely associated with HCC progression.More effort is needed for exploring the prognostic value of lncRNAs in HCC base on The Cancer Genome Atlas(TCGA).The present study aimed to develop a robust lncRNA signature associated with HCC overall survival(OS).METHODS lncRNAs expression profiles and corresponding clinical information for HCC cases were acquired from TCGA.We obtained differential expressed lncRNA(DElncRNA)between tumor and paratumor tissues via R packages.Univariate Cox regression analysis was performed to screen the lncRNAs significantly associated with OS for the least absolute shrinkage and selection operator(LASSO)modelling.The established lncRNA signature was developed and validated.RESULTS We identified 1292 DElncRNAs,and 142 lncRNAs were significant in univariate Cox regression analysis(P<0.05).LASSO regression confirmed nine lncRNAs out of 142 lncRNAs including AC010547.1,AC034229.4,AL121721.1,AP003390.1,BBOX1-AS1,LINC00462,LINC00942,LINC01353,and LINC01954.Then,the prognostic risk score was calculated.This risk model was significantly associated with the OS of HCC with a hazard ratio(HR)being 2.60(95%CI:2.18-3.21)and log-rank P-value being 1.72 e-6.CONCLUSIONS We have constructed a nine-lncRNA signature for prognosis prediction of HCC.The lncRNAs in this risk model provides new clinical evidence for the targeted treatment of HCC.