Identification and analysis of immune-related subtypes of hepatocellular carcinoma
Identification and analysis of immune-related subtypes of hepatocellular carcinoma
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DOI：
10.1177/1535370220970130
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发表时间：
2021-03-01
影响因子：
3.2
通讯作者：
Yu, Min
中科院分区：
文献类型：
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作者：
Wang, Qimeng;Huang, Jin;Yu, Min
肝细胞癌是一种难以治愈的恶性肿瘤。免疫治疗在多种难治性恶性肿瘤中显示出潜在的应用价值。由于肝癌免疫微环境的复杂性，肝癌免疫治疗的疗效并不如预期。使用来自TCGA和ICGC数据库的肝细胞癌表达数据对肝细胞癌亚型进行分类和验证。通过基因集富集分析鉴定免疫相关功能和途径，同时使用CIBERSORT算法估计表示免疫细胞亚群的部分。免疫低（Immunity_L）、免疫中（Immunity_M）和免疫高（Immunity_H）被指定为肝细胞癌的三种免疫相关亚型。与其他亚型相比，免疫_H中基质细胞和免疫细胞的数量最多。有趣的是，从Immunity_L到Immunity_H，M0巨噬细胞的比例降低，而CD 8 T细胞的比例增加。此外，HLA基因表达水平以及六种免疫检查点基因的表达水平在Immunity_L中显著低于Immunity_H。对Immunity_L和Immunity_H之间的1512个差异表达基因进行功能分析。最后，构建了具有118个节点的PPI网络。连接度最高的节点是B2 M、HLA-DRB和HLA-DRB 1。上述结果在ICGC-JP和ICGC-FR数据库中得到验证，趋势一致。在这项研究中，我们将肝细胞癌分为三个亚型，并探讨这些亚型的免疫相关特征。这些结果可能为肝癌的免疫治疗提供新的思路。
Hepatocellular carcinoma is a malignance that remains difficult to cure. Immunotherapy has shown its potential application in a variety of refractory malignancies. Due to the complexity of immune microenvironment of hepatocellular carcinoma, the efficacy of immunotherapy for hepatocellular carcinoma is not as effective as expected. Expression data of hepatocellular carcinoma from the TCGA and ICGC databases were used for classification and verification of hepatocellular carcinoma subtypes. The immune-related functions and pathways were identified via gene set enrichment analysis, while the sections denoting the subsets of the immune cells were estimated using the CIBERSORT algorithm. Immunity low (Immunity_L), immunity medium (Immunity_M), and immunity high (Immunity_H) were specified as the three immune-related subtypes of hepatocellular carcinoma. The quantity of stromal and immune cells was the most substantial in Immunity_H, compared to the other subtypes. Interestingly, the proportion of M0 macrophages decreased from Immunity_L to Immunity_H, while the proportion of CD8 T cells increased. Furthermore, the HLA genes expression levels, as well as those of six immune checkpoint genes were substantially lower in Immunity_L than in Immunity_H. Functional analysis was performed for 1512 differentially expressed genes between Immunity_L and Immunity_H. Finally, the PPI network was constructed with 118 nodes. The highest connectivity degree nodes were B2M, HLA-DRA, and HLA-DRB1. The above results were verified in ICGC-JP and ICGC-FR databases with a consistent trend. In this study, we divided hepatocellular carcinoma into three subtypes and explored the immune-related characteristics of these subtypes. These results may provide new insights for immunotherapy of hepatocellular carcinoma.