RNA结合蛋白对肝癌预后和免疫浸润的评估价值  

RNA binding protein signature for the evaluation of prognosis and immune infiltration of hepatocellular carcinoma

作　　者：陈苗 张家康 李述捷 易永祥 CHEN Miao;ZHANG Jia-kang;LI Shu-jie;YI Yong-xiang(The Second Hospital of Nanjing,Nanjing University of Chinese Medicine,Nanjing 210003,China)

机构地区：[1]南京中医药大学附属南京医院,江苏南京210003

出　　处：《生物技术》2023年第1期111-120,110,共11页Biotechnology

基　　金：江苏省临床医学科技专项-新型临床诊疗技术攻关项目(BL2014005);江苏省研究生科研与实践创新计划(KYCX21-1635)。

摘　　要：[目的]探索RNA结合蛋白(RBP)在肝癌预后以及免疫浸润中的评估价值。[方法]下载TCGA数据库中肝癌(LIHC)数据,筛选出差异表达的RBP基因。利用LASSO和多因素COX构建风险模型,Kaplan-Meier方法比较高低风险组患者的预后。对高低风险组患者的差异基因进行功能富集分析。利用GSVA分析高低风险组免疫浸润,并比较两组患者药物敏感性和免疫治疗反应性。[结果]总共得到330个差异基因,LASSO-COX回归模型最终纳入6个基因(UPF3B、MRPL54、ZC3H13、DHX58、PPARGC1A、EIF2AK4)。高风险组患者总体生存率劣于低风险组患者(P<0.05)。风险模型预测患者总体生存率的AUROC在TCGA和ICGC中分别为0.756和0.781。免疫浸润分析提示高风险组调节T细胞富集量高于低风险组,而NK细胞则较低。两组患者对索拉非尼、多西他赛、顺铂敏感性有明显差异(P<0.05),且低风险组对免疫治疗更敏感。[结论] RBP风险模型可有效评估肝癌患者的预后、免疫浸润状态、化疗药物及免疫治疗的敏感性,可能为肝癌患者的风险分级和免疫治疗带来新的思路。[Objective]To explore the significance of RNA binding protein(RBP) in the prognosis and immune infiltration evaluation of hepatocellular carcinoma(HCC).[Method]Data of HCC patients were downloaded from the TCGA database, differentially expressed RBP genes were screened out. The prognostic genes were filtered by LASSO-COX regression analysis, and risk models were constructed. Kaplan-Meier method was used to compare the outcomes of patients in high-and low-risk groups. Functional enrichment analysis was performed for differential genes between high-and low-risk groups. GSVA was used to analyze the immune infiltration of the high-and low-risk groups. In addition, drug sensitivity and immunotherapy response were also compared between groups.[Result] 330 RBPs were differentially expressed in liver cancer and adjacent tissues. The risk model included six genes(UPF3B, MRPL54, ZC3H13, DHX58, PPARGC1A, EIF2AK4). Survival analysis showed that the prognosis of patients in the high-risk group was worse than that in the low-risk group(P<0.05). The area under the receiver operating characteristic curve(AUROC) for predicting the overall survival of patients by risk value in TCGA and ICGC were 0.756 and 0.781, respectively, indicating that the model had a good prognostic value. Immune infiltration analysis showed that the concentration of regulated T cells in the high-risk group was higher than that in the low-risk group, while the enrichment of NK cells in high-risk group was relatively low. Drug sensitivity analysis indicated the high-and low-risk group had significantly different sensitivity of sorafenib, docetaxel, and cisplatin.Moreover, low-risk group was more sensitive to immunotherapy.[Conclusion]The RBP risk model can effectively evaluate the prognosis, immune infiltration, chemotherapy sensitivity, and immune check point inhibitors(ICPs) repsonse of HCC patients, which may bring new ideas for the risk stratification and immune therapy of HCC patients.

关 键 词：肝癌 RNA结合蛋白 列线图 TCGA 免疫浸润 

分 类 号：R735.7[医药卫生—肿瘤]