Xiao Han, Wang Ben, Xiong Hai-Xia, Guan Jia-Fu, Wang Jian, Tan Tao, Lin Kang, Zou Shu-Bing, Hu Zhi-Gang, Wang Kai
Hepato-Biliary-Pancreatic Surgery Division, Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China.
J Cell Physiol. 2021 Apr;236(4):2572-2591. doi: 10.1002/jcp.30015. Epub 2020 Aug 27.
Changes in immune responses to hepatocellular carcinoma (HCC) are closely related to the occurrence, development, and prognosis of this disease. Exploring the role of immune-related genes (IRGs) in HCC would provide insights into the mechanisms regulating this disease. The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) provide a platform for such research, owing to a large number of HCC samples available for comprehensive and systematic immunogenomics analyses. We analyzed the IRGs expression profile and clinical information of patients with HCC based on the TCGA and ICGC database. Potential molecular mechanisms and properties of the screened IRGs were analyzed across multiple databases. And we analyzed the correlation between IRGs, single-nucleotide polymorphisms, and copy number variation. A novel prognostic index, based on IRGs, was developed using the LASSO Cox regression algorithm, followed by univariate and multivariate Cox regression analyses to analyze the prognostic index. Information in the ICGC database was used to verify the reliability of the prognostic index. A total of 54 differentially expressed IRGs were found to be significantly associated with HCC prognosis, and there is a significant correlation between their expression level and copy number variation. Functional enrichment analyses indicated that the genes play active roles in tumor and immune-related signaling pathways. In addition, five potential biomarkers namely IRG, MAPK3, HSP90AA1, HSP90AB1, HSPA4, and CDK4, were identified. Finally, a novel prognostic index, based on IRGs (PSMD14, FABP6, ISG20L2, HGF, BIRC5, IL17D, and STC2), was found useful as an independent prognostic factor, not only for prognosis but also to reflect levels of infiltration in a variety of immune cells. Our team conducted a genomics study of IRGs in HCC and screened several clinically significant IRGs, and our model provides an effective approach for stratification and characterization of patients using IRG-based immunolabeling tools to monitor the prognosis of HCC.
对肝细胞癌（HCC）免疫反应的变化与该疾病的发生、发展及预后密切相关。探索免疫相关基因（IRGs）在HCC中的作用将有助于深入了解调控该疾病的机制。癌症基因组图谱（TCGA）和国际癌症基因组联盟（ICGC）提供了这样一个研究平台，因为有大量的HCC样本可用于全面系统的免疫基因组学分析。我们基于TCGA和ICGC数据库分析了HCC患者的IRGs表达谱及临床信息。通过多个数据库分析筛选出的IRGs的潜在分子机制和特性。并且我们分析了IRGs、单核苷酸多态性和拷贝数变异之间的相关性。使用LASSO Cox回归算法建立了基于IRGs的新型预后指数，随后进行单因素和多因素Cox回归分析以分析该预后指数。利用ICGC数据库中的信息验证预后指数的可靠性。共发现54个差异表达的IRGs与HCC预后显著相关，且它们的表达水平与拷贝数变异之间存在显著相关性。功能富集分析表明这些基因在肿瘤和免疫相关信号通路中发挥积极作用。此外，还鉴定出了五个潜在的生物标志物，即IRG、MAPK3、HSP90AA1、HSP90AB1、HSPA4和CDK4。最后，发现基于IRGs（PSMD14、FABP6、ISG20L2、HGF、BIRC5、IL17D和STC2）的新型预后指数作为独立的预后因素不仅对预后有意义，而且还能反映多种免疫细胞的浸润水平。我们团队对HCC中的IRGs进行了基因组学研究并筛选出了几个具有临床意义的IRGs，我们的模型为使用基于IRG的免疫标记工具对患者进行分层和特征化以监测HCC的预后提供了一种有效方法。
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