Ye Dingde, Liu Yaping, Li Guoqiang, Sun Beicheng, Peng Jin, Xu Qingxiang
Nanjing Drum Tower Hospital, Medicine School of Southeast University, Nanjing, China.
School of Life Science and Technology, Southeast University, Nanjing, China.
Front Oncol. 2021 Nov 19;11:766072. doi: 10.3389/fonc.2021.766072. eCollection 2021.
Hepatocellular carcinoma (HCC) is one of the malignant tumors with high morbidity and mortality worldwide. Immunotherapy has emerged as an increasingly important cancer treatment modality. However, the potential relationship between immune genes and HCC still needs to be explored. The purpose of this study is to construct a new prognostic risk signature to predict the prognosis of HCC patients based on the expression of immune-related genes (IRGs) and explore its potential mechanism.
We analyzed the gene expression data of 332 HCC patient samples and 46 adjacent normal tissues samples (Solid Tissue Normal including cirrhotic tissue) in The Cancer Genome Atlas (TCGA) database and clinical characteristics. We analyzed the gene expression data, identified differentially expressed IRGs in HCC tissues, filtered IRGs with prognostic value to construct an IRG signature, and classified patients into high and low gene expression groups based on the expression of IRGs in their tumor tissues. We also investigated the potential molecular mechanisms of IRGs through a bioinformatics approach using Protein-Protein Interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG) database analysis and Gene Ontology (GO) database analysis. Differentially expressed IRGs associated with significant clinical outcomes (SIRGs) were identified by univariate Cox regression analysis. An immune-related risk score model (IRRSM) was established based on Lasso Cox regression analysis and multivariate Cox regression analysis. Based on the IRRSM, the immune score of the patients was calculated, and the patients were divided into high-risk and low-risk patients according to the median score, and the differences in survival between the two groups were compared. Then, the correlation analysis between the IRRSM and clinical characteristics was performed, and the IRRSM was validated using the International Cancer Genome Consortium (ICGC) database.
The IRRSM was eventually constructed and confirmed to be an independent prognostic model for HCC patients. The IRRSM was shown to be positively correlated with the infiltration of four types of immune cells.
Our results showed that some SIRGs have potential value for predicting the prognosis and clinical outcomes of HCC patients. IRGs affect the prognosis of HCC patients by regulating the tumor immune microenvironment (TIME). This study provides a new insight for immune research and treatment strategies in HCC patients.
肝细胞癌(HCC)是全球发病率和死亡率较高的恶性肿瘤之一。免疫疗法已成为一种越来越重要的癌症治疗方式。然而,免疫基因与HCC之间的潜在关系仍有待探索。本研究的目的是基于免疫相关基因(IRGs)的表达构建一种新的预后风险特征,以预测HCC患者的预后,并探索其潜在机制。
我们分析了癌症基因组图谱(TCGA)数据库中332例HCC患者样本和46例相邻正常组织样本(包括肝硬化组织的实体组织正常样本)的基因表达数据及临床特征。我们分析基因表达数据,鉴定HCC组织中差异表达的IRGs,筛选具有预后价值的IRGs以构建IRG特征,并根据肿瘤组织中IRGs的表达将患者分为高基因表达组和低基因表达组。我们还通过使用蛋白质-蛋白质相互作用(PPI)网络、京都基因与基因组百科全书(KEGG)数据库分析和基因本体论(GO)数据库分析的生物信息学方法研究IRGs的潜在分子机制。通过单变量Cox回归分析鉴定与显著临床结局相关的差异表达IRGs(SIRGs)。基于套索Cox回归分析和多变量Cox回归分析建立免疫相关风险评分模型(IRRSM)。基于IRRSM计算患者的免疫评分,并根据中位数评分将患者分为高风险和低风险患者,比较两组之间的生存差异。然后,进行IRRSM与临床特征之间的相关性分析,并使用国际癌症基因组联盟(ICGC)数据库对IRRSM进行验证。
最终构建了IRRSM,并证实其为HCC患者的独立预后模型。IRRSM与四种免疫细胞的浸润呈正相关。
我们的结果表明,一些SIRGs对预测HCC患者的预后和临床结局具有潜在价值。IRGs通过调节肿瘤免疫微环境(TIME)影响HCC患者的预后。本研究为HCC患者的免疫研究和治疗策略提供了新的见解。