Feng Xiaofei, Mu Shanshan, Ma Yao, Wang Wenji
Department of Orthopedics, Lanzhou University First Affiliated Hospital, Lanzhou, China.
Pediatric Rheumatism Immunology Department, Lanzhou University Second Hospital, Lanzhou, China.
Front Mol Biosci. 2021 Oct 1;8:715728. doi: 10.3389/fmolb.2021.715728. eCollection 2021.
With the increasing prevalence of Hepatocellular carcinoma (HCC) and the poor prognosis of immunotherapy, reliable immune-related gene pairs (IRGPs) prognostic signature is required for personalized management and treatment of patients. Gene expression profiles and clinical information of HCC patients were obtained from the TCGA and ICGC databases. The IRGPs are constructed using immune-related genes (IRGs) with large variations. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct IRGPs signature. The IRGPs signature was verified through the ICGC cohort. 1,309 IRGPs were constructed from 90 IRGs with high variability. We obtained 50 IRGPs that were significantly connected to the prognosis and constructed a signature that included 17 IRGPs. In the TCGA and ICGC cohorts, patients were divided into high and low-risk patients by the IRGPs signature. The overall survival time of low-risk patients is longer than that of high-risk patients. After adjustment for clinical and pathological factors, multivariate analysis showed that the IRGPs signature is an independent prognostic factor. The Receiver operating characteristic (ROC) curve confirmed the accuracy of the signature. Besides, gene set enrichment analysis (GSEA) revealed that the signature is related to immune biological processes, and the immune microenvironment status is distinct in different risk patients. The proposed IRGPs signature can effectively assess the overall survival of HCC, and provide the relationship between the signature and the reactivity of immune checkpoint therapy and the sensitivity of targeted drugs, thereby providing new ideas for the diagnosis and treatment of the disease.
随着肝细胞癌（HCC）患病率的增加以及免疫治疗预后不佳，个性化管理和治疗患者需要可靠的免疫相关基因对（IRGP）预后特征。从TCGA和ICGC数据库中获取HCC患者的基因表达谱和临床信息。使用具有较大变异的免疫相关基因（IRG）构建IRGP。采用最小绝对收缩和选择算子（LASSO）回归分析构建IRGP特征。通过ICGC队列验证了IRGP特征。从90个具有高变异性的IRG中构建了1309个IRGP。我们获得了50个与预后显著相关的IRGP，并构建了一个包含17个IRGP的特征。在TCGA和ICGC队列中，根据IRGP特征将患者分为高风险和低风险患者。低风险患者的总生存时间长于高风险患者。在调整临床和病理因素后，多变量分析表明IRGP特征是一个独立的预后因素。受试者工作特征（ROC）曲线证实了该特征的准确性。此外，基因集富集分析（GSEA）表明该特征与免疫生物学过程相关，不同风险患者的免疫微环境状态不同。所提出的IRGP特征可以有效评估HCC的总生存，并提供该特征与免疫检查点治疗反应性和靶向药物敏感性之间的关系，从而为该疾病的诊断和治疗提供新思路。
