肝癌细胞周期调控相关基因预后模型构建与评估  

CONSTRUCTION AND EVALUATION OF PROGNOSTIC MODEL FOR HEPATOCELLULAR CARCINOMA BASED ON CELL CYCLE REGULATION-ASSOCIATED GENES

作　　者：孙东旭 朱文静 金志朋 刘华元 朱朋程 史光军[3] SUN Dongxu;ZHU Wenjing;JIN Zhipeng;LIU Huayuan;ZHU Pengcheng;SHI Guangjun(Graduate School,Dalian Medical University,Dalian 116000,China)

机构地区：[1]大连医科大学研究生院,辽宁大连116000 [2]青岛大学附属青岛市市立医院肝胆外科 [3]青岛大学青岛医学院

出　　处：《青岛大学学报（医学版）》2022年第2期205-212,共8页Journal of Qingdao University(Medical Sciences)

基　　金：山东省自然科学基金面上项目(ZR202103030420)。

摘　　要：目的 基于细胞周期调控相关基因构建新的肝癌预后模型,为预测肝癌的预后及肿瘤治疗提供新的思路和方向。方法 肝癌病人的mRNA表达谱和临床数据收集于TCGA肿瘤数据库、GEO基因表达数据库和ICGC肿瘤基因数据库。通过R软件分析筛选肝癌的差异表达基因,并通过通路与基因功能富集(PPEA)方法确定与细胞周期相关的基因集。使用单因素Cox回归分析和Kaplan-Meier曲线联合确定与肝癌预后相关的细胞周期调控基因,使用Lasso Cox回归模型构建和验证肝癌预后模型。最后使用3对临床样本进行二代测序验证基因表达水平。结果 通过差异筛选和基因富集分析以及单因素Cox回归分析,找到24个细胞周期调控基因与肝癌病人预后相关(HR>1,FDR<0.05)。Lasso Cox回归构建的肝癌预后模型评估结果显示,高风险组的总生存期(OS)显著小于低风险组(TCGA-LIHC构建队列P<0.001,LIRI-JP验证队列P<0.001);风险评分是OS的独立预后因素(HR>1,P<0.001)。临床样本测序结果验证显示,大部分肝癌细胞周期调控预后基因在肝癌组织中存在显著高表达。结论 本研究构建了细胞周期调控相关基因的肝癌病人预后模型,为肝癌病人的预后预测和治疗提供新的思路和分子治疗靶点。Objective To construct a new prognostic model for hepatocellular carcinoma(HCC) patients based on cell cycle regulation-associated genes, and to provide a new idea and method for predicting the prognosis and treatment of HCC. Methods The mRNA expression profile and clinical data of HCC patients were collected from TCGA, GEO, and ICGC databases. Differentially expressed genes were screened out using R software, and the gene sets related to cell cycle were identified by pathway and gene set enrichment analysis. Univariate Cox regression analysis and Kaplan-Meier curve were used to identify the cell cycle regulation genes associated with the prognosis of HCC. The Lasso Cox regression model was used to construct and verify the prognostic model of HCC. Finally, three pairs of clinical samples were subjected to next-generation sequencing to verify gene expression levels. Results Through differential screening, gene enrichment analysis, and univariate Cox regression analysis, 24 cell cycle regulation genes were found to be associated with prognosis of HCC patients(HR>1, false discovery rate <0.05). The prognostic model for HCC constructed by Lasso Cox regression showed that the overall survival(OS) of the high-risk group was significantly lower than that of the low-risk group(TCGA-LIHC cohort P<0.001, LIRI-JP cohort P<0.001);risk score was an independent predictor of OS(HR>1,P<0.001). The results of clinical sample sequencing showed that most of the cell cycle regulation genes associated with the prognosis of HCC were significantly overexpressed in HCC tissues. Conclusion In this study, a prognostic model of HCC patients related to cell cycle regulation-associated genes was constructed, providing new ideas and molecular therapeutic targets for the prognostic prediction and treatment of HCC patients.

关 键 词：癌 肝细胞 细胞周期 预后 计算生物学 转录组测序技术 

分 类 号：R735.7[医药卫生—肿瘤]