肝癌预后模型的构建及其在免疫治疗中的作用研究  

The Construction of a Prognostic Model for Hepatocellular Carcinoma and its Role in Immunotherapy

作　　者：李一鸣 陈文翔 王禹 何俊 周剑寅[1] LI Yi-ming;CHEN Wen-xiang;WANG Yu;HE Jun;ZHOU Jian-yin(Department of Hepatobiliary and Pancreatic Surgery,Zhongshan Hospital Xiamen University,Xiamen 361005,Fujian,China)

机构地区：[1]厦门大学附属中山医院肝胆胰外科,福建厦门361005

出　　处：《医学信息》2022年第4期68-74,共7页Journal of Medical Information

基　　金：福建省医学创新课题(编号:2019-CXB-36);福建省自然科学基金(编号:2019J01551);厦门市医疗卫生重点项目(编号:3502Z20191106)。

摘　　要：目的长非编码RNA (lncRNAs)在肝细胞癌(HCC)的发生发展中起重要作用,寻找可能的基因组不稳定性相关lncRNAs(GI-lncRNAs),建立可以预测HCC患者总体生存率的预后模型。方法利用肿瘤基因组图谱数据库(TCGA)的肝细胞癌患者的表达数据、临床资料及突变数据,根据不稳定性计算模型,筛选GI-lncRNAs;进行层次聚类验证后,采用单因素和多因素Cox分析建立预后模型,在对预测的可靠性进行评估后,根据预后模型,进行风险亚组间免疫特点、ICI治疗及化学治疗综合分析。结果共鉴定出88个GI-lncRNAs,建立基于4个GI-lncRNAs(MIR210HG、LUCAT1、AC245041.2、AC010643.1)的风险评分模型;风险评分是肝癌患者的独立预后因子,可用于预测患者预后及肿瘤分级和分期情况;风险亚组间存在体细胞突变及免疫特征差异;风险评分与CD274、CTLA4、HAVCR2、IFNG、PDCD1、TNF的高表达呈正相关,且高风险组样品对阿霉素、丝裂霉素C更加敏感。结论基于基因组不稳定性相关lncRNAs的预后模型可以预测肝细胞癌患者的预后。Objective Long non-coding RNA(lncRNAs) plays an important role in the development of hepatocellular carcinoma(HCC),to find possible genomic instability related lncRNAs(GI-lncRNAs),and to establish a prognostic model that can predict the overall survival rate of HCC patients.Methods The expression data,clinical data and mutation data of patients with hepatocellular carcinoma in the tumor genome atlas database(TCGA) were used to screen GI-lncRNAs according to the instability calculation model.After hierarchical clustering verification,the prognosis model was established by single-factor and multi-factor Cox analysis.After evaluating the reliability of the prediction,the comprehensive analysis of immune characteristics,ICI treatment and chemotherapy among risk subgroups was carried out according to the prognosis model.Results A total of 88 GIlncRNAs were identified,and a risk score model based on four GI-lncRNAs(MIR210 HG,LUCAT1,AC245041.2,AC010643.1) was established.Risk score was an independent prognostic factor for patients with liver cancer,which could be used to predict the prognosis of patients,tumor grading and staging.There were differences in somatic mutations and immune characteristics among risk subgroups;the risk score was positively correlated with the high expression of CD274,CTLA4,HAVCR2,IFNG,PDCD1 and TNF,and the samples in the high-risk group were more sensitive to adriamycin and mitomycin C.Conclusion The prognosis model based on lncRNAs associated with genomic instability can predict the prognosis of patients with hepatocellular carcinoma.

关 键 词：长链非编码RNA 肝细胞癌 预后模型 免疫治疗 

分 类 号：R735.7[医药卫生—肿瘤]