A novel prognostic index of hepatocellular carcinoma based on immunogenomic landscape analysis
A novel prognostic index of hepatocellular carcinoma based on immunogenomic landscape analysis
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基于免疫基因组图谱分析的肝细胞癌新预后指标
DOI：
10.1002/jcp.30015
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发表时间：
2020-08-27
影响因子：
5.6
通讯作者：
Wang, Kai
中科院分区：
文献类型：
--
作者：
Xiao, Han;Wang, Ben;Wang, Kai
肝细胞癌（HCC）免疫应答的改变与HCC的发生、发展及预后密切相关。探索免疫相关基因（IRGs）在HCC中的作用将为了解这种疾病的调控机制提供新的见解。癌症基因组图谱（TCGA）和国际癌症基因组联盟（ICGC）为此类研究提供了一个平台，因为有大量的HCC样本可用于全面和系统的免疫基因组学分析。我们基于TCGA和ICGC数据库分析了肝癌患者的IRGs表达谱和临床信息。在多个数据库中分析了筛选的IRG的潜在分子机制和性质。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。一种新的预后指数，IRGs的基础上，开发使用LASSO考克斯回归算法，然后通过单变量和多变量考克斯回归分析的预后指数。ICGC数据库中的信息用于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，并且其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，还鉴定了5种潜在的生物标志物，即IRG、MAPK3、HSP90AA1、HSP90AB1、HSPA4和CDK4。最后，发现一种基于IRG（PSMD 14、FABP 6、ISG 20 L2、HGF、BIRC 5、IL 17 D和STC 2）的新型预后指数可用作独立的预后因素，不仅用于预后，而且还反映各种免疫细胞的浸润水平。我们的团队对HCC中的IRGs进行了基因组学研究，并筛选了几个具有临床意义的IRGs，我们的模型为使用基于IRGs的免疫标记工具对患者进行分层和表征提供了有效的方法，以监测HCC的预后。
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.