SRPRB在肝细胞癌中的表达及预后风险模型的建立  

Expression of SRPRB in Hepatocellular Carcinoma and Establishment of Prognostic Risk Model

作　　者：舒思远 孟涛 周扬刘 童钟 SHU Si-yuan;MENG Tao;ZHOU Yang-liu;TONG Zhong(Department of Hepatobiliary Surgery,the Third Affiliated Hospital of Anhui Medical University,Hefei 230061;The Fifth Clinical Medical College of Anhui Medical University,Hefei 230031;Department of General Surgery,the First Afiliated Hospital of Anhui Medical University,Hefei 230022,China)

机构地区：[1]安徽医科大学第三附属医院肝胆外科,合肥230002 [2]安徽医科大学第五临床医学院,合肥230031 [3]安徽医科大学第一附属医院普外科,合肥230022

出　　处：《肝胆外科杂志》2024年第2期134-143,共10页Journal of Hepatobiliary Surgery

摘　　要：目的探索SRPRB在肝细胞癌(hepatocellular carcinoma,HCC)患者中的表达水平及与预后的关系,并基于其共表达的免疫相关基因构建HCC临床预后风险模型。方法本研究从TCGA数据库中获取HCC患者的表达谱和临床信息。采用Kaplan-Meier法、"pROC"包分析SRPRB与HCC患者生存预后的关系。实时荧光定量PCR及免疫组化验证SRPRB在HCCmRNA和蛋白水平表达情况。采用Spearman相关分析确定SRPRB的共表达基因,与ImmPort数据库获取的免疫相关基因取交集获得HCC患者SRPRB共表达免疫相关基因。并通过GO富集分析、KECG通路分析确定这些基因参与的生物学过程及功能。将TCGA数据库中的患者按5:5比例随机分为训练集和内部验证集,以GEO数据库中的HCC患者作为外部验证集。随后利用Cox回归筛选基因来构建预后模型,利用Kaplan-Meier生存曲线、ROC曲线评估风险模型对HCC的预测价值,并基于预测模型建立列线图。结果SRPRB在HCC组织中的表达量显著高于正常组织,K-M曲线显示,高表达SRPRB的患者总生存率比低表达组差。功能富集分析显示,SRPRB共表达免疫相关基因主要参与受体配体活性、免疫受体活性、抗原处理和呈递、自然杀伤细胞介导的细胞毒性作用、Toll样受体信号通路等信号通路。单因素和多因素Cox回归分析共筛选出7个SRPRB相关免疫预后基因,构建包括七个基因(SLC29A3、IKBKE、ISG20L2、PSMD6、CXCL8、TEK、EED)的风险模型,Kaplan-Meier生存曲线表明,训练集、内部验证集和外部验证集中的高风险组患者预后更差(P<0.01)。训练集中1年、2年和3年AUC值分别为0.819.0.812和0.803、内部验证集中1年、2年和3年AUC值分别为0.739、0.623和0.692且外部验证集中1年、2年和3年AUC值分别为0.608、0.653和0.610。该模型可作为独立预测因素评估HCC患者的预后,基于风险评分构建的列线图具有更好的区分能力和一致性。结论仑SRPRB高表达与HCC的Objective To investigate the expression level of SRPRB in hepatocellular carcinoma(HCC)patients and its rela-tionship with prognosis,and to construct a clinical prognostic risk model for HCC based on its co-expressed immune-related genes.Methods In this study,expression profiles and clinical information of HCC patients were obtained from the TCGA database.The rela-tionship between SRPRB and survival prognosis of HCC patients was analysed using the Kaplan-Meier method and the"pROC"pack-age.Real-time fluorescence quantitative PCR and immunohistochemistry were used to verify the expression of SRPRB in HCC mRNA and protein levels.Spearman correlation analysis was used to identify the co-expressed genes of SRPRB,and intersected with the im-mune-related genes obtained from the ImmPort database to obtain the co-expressed immune-related genes of SRPRB in HCC patients.The biological processes and functions involved in these genes were also determined by GO enrichment analysis and KEGG pathway a-nalysis.The patients in the TCGA database were randomly divided into a training set and an internal validation set in a 5:5 ratio,and the HCC patients in the CEO database were used as an external validation set.Then,Cox regression was used to screen the genes to construct the prognostic model,and the predictive value of the risk model for HCC was evaluated using Kaplan-Meier survival curves and ROC curves,and a column-line diagram was constructed based on the predictive model.Results The expression of SRPRB in HCC tissues was significantly higher than that in normal tissues,and the K-M curves showed that the overall survival rate of patients with high expression of SRPRB was worse than that of the low expression group.Functional enrichment analysis showed that SRPRB co-expressed immune-related genes were mainly involved in signaling pathways such as receptor ligand activity,immune receptor activity,antigen processing and presentation,natural killer cell-mediated cytotoxicity and Toll-like receptor signaling pathway.A total of seven

关 键 词：肝细胞肝癌 SRPRB 免疫 TCGA 预后模型 

分 类 号：R735.7[医药卫生—肿瘤]