肝癌免疫浸润联合RNA结合蛋白和转录因子预后指标的构建分析  

Prognostic index construction and analysis of immune infiltration combined with RNA binding protein and transcription factor in hepatocellular carcinoma

作　　者：王鹏辉 冯国勋[1] 俞巍[1] 张洪义 Wang Penghui;Feng Guoxun;Yu Wei;Zhang Hongyi(Department of General Surgery,Beijing Tiantan Hospital,Capital Medical University,Beijing100070,China)

机构地区：[1]首都医科大学附属北京天坛医院普通外科,北京100070

出　　处：《中华肝胆外科杂志》2022年第9期656-661,共6页Chinese Journal of Hepatobiliary Surgery

摘　　要：目的全面分析肝癌的RNA结合蛋白和转录因子基因表达及免疫浸润对肝癌预后的预测价值。方法在癌症基因组图谱(TCGA)(n=365)、基因表达综合数据库GSE54236(n=78)和GSE14520(n=221)中筛选RNA结合蛋白和转录因子的共同基因集,单因素Cox回归分析进行初筛,通过LASSO-Cox构建生存回归模型,通过标准化得到整合RNA结合蛋白和转录因子的复合指数CIRT,根据其中位数将肝癌患者分为CIRT^(high)组(n=182)和CIRTlow组(n=182),并分析两组免疫浸润等差异。结果共筛选出37个预后相关的RNA结合蛋白和转录因子基因,通过LASSO-Cox构建基于其中7个最相关基因的预后预测模型。CIRT^(high)组患者的M1型巨噬细胞(P=0.032)、M2型巨噬细胞(P=0.009)、静息肥大细胞(P<0.001)、活化自然杀伤细胞(P=0.007)和静息记忆CD4+T细胞水平较低(P<0.001),而CIRTlow组的静息树突状细胞(P=0.048)、M0型巨噬细胞(P<0.001)、中性粒细胞(P=0.049)、滤泡辅助性T细胞(P=0.004)和调节性T细胞(P=0.001)水平较低,差异具有统计学意义。基因富集分析显示,CIRT^(high)组的TCGA和GSE14520在细胞周期、DNA修复过程中高度富集。在TCGA队列中,CIRTlow组的患者比CIRT^(high)组的患者总生存更优。对TCGA队列中5年随访数据进行分析,CIRT对于肝癌患者长期生存预后具有良好的预测价值(受试者工作特征曲线下面积0.71)。结论在肝癌中建立了基于RNA结合蛋白和转录因子表达谱以及免疫细胞浸润的新的预后指标,CIRT可以作为一个独立的预后预测指标。Objective To comprehensively analyze the prognostic prediction value of RNA binding protein,transcription factor gene expression and immune infiltration in hepatocellular carcinoma(HCC).Methods Common gene sets associated with RNA-binding proteins and transcription factors were screened in TCGA(n=365),GSE54236(n=78)and GSE14520(n=221)datasets.Univariate Cox regression was used for primary screening.The survival regression model was constructed by LASSO-Cox.And a complex index[CIRT=(score-min)/max]was calculated.According to the median of CIRT,the HCC patients were divided into CIRT^(high) group(n=182)and CIRTlow group(n=182).The differences of prognosis,immune infiltration between the two groups were analyzed.Results Of 37 prognostically relevant RNA binding protein and transcription factor genes were identified.The prognosis prediction model based on seven selected genes was determined by stepwise regression.Patients in the CIRT^(high) group exhibited a lower percentage of macrophages in M1(P=0.032),macrophages in M2(P=0.009),resting mast cell(P<0.001),activated NK cells(P=0.007),and resting memory CD4+T cells(P<0.001),while patients in the CIRTlow group showed a lower level of resting dendritic cells(P=0.048),macrophages in M0(P<0.001),neutrophils(P=0.049),follicular helper T cells(P=0.004)and regulatory T cells(P=0.001).GSEA analysis has shown that CIRT^(high) groups were highly enriched in cell cycle,DNA repair pathways in TCGA and GSE14520.In the TCGA cohort,the CIRTlow group had better overall survival than the CIRT^(high) group.Analysis of 5-year follow-up data in the TCGA cohort showed that CIRT had a good predictive value for long-term survival of patients with liver cancer(area under receiver operating characteristic curve was 0.71).Conclusion A novel prognostic index and classifier based on RNA-binding protein expression,transcription factors and immune expression profiles were developed and cross-cohort validated.CIRT could be used as an independent predictor.

关 键 词：癌 肝细胞 预后生物标志物 免疫浸润 RNA结合蛋白 转录因子 

分 类 号：R735.7[医药卫生—肿瘤]