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Identification of immunological subtypes of hepatocellular carcinoma with expression profiling of immune-modulating genes.

用免疫调节基因表达谱鉴定肝细胞癌的免疫学亚型。

  • 影响因子:5.5150
  • DOI:10.18632/aging.103395
  • 作者列表:"Cao D","Chen MK","Zhang QF","Zhou YF","Zhang MY","Mai SJ","Zhang YJ","Chen MS","Li XX","Wang HY
  • 发表时间:2020-06-16
Abstract

:Recent studies demonstrate that immune checkpoint inhibitor (ICI) therapy has achieved success in many types of advanced cancers including advanced hepatocellular carcinoma (HCC). However, ICI therapy is beneficial in only some HCC patients, suggesting that immune-responses are highly variable in HCCs. Therefore, understanding the immune status in HCC microenvironment will facilitate ICI immunotherapy and guide patient selection for the therapy. In this study, we first analyzed the expression profile of immune-modulating genes and their relationship with survival of HCC patients using the data downloaded from The Cancer Genome Atlas - Liver Hepatocellular Carcinoma (TCGA-LIHC) database, and found that the higher expressions of CD276 (B7-H3) and CD47 were significantly associated with poor survival. Then we identified 4 immune subtypes of HCCs with different survivals by using the combination expression of B7-H3 (or CD47) and CD8. Patients with B7-H3low/CD8high or CD47low/CD8high have the best survival while ones with B7-H3high/CD8low or CD47high/CD8low have the worst survival. The 4 immune subtypes were validated in another 72 HCC patients obtained from South China. In conclusion, our findings suggest that HCC patient prognosis is associated with immunophenotypes by T cell infiltration (CD8 expression) and the expression of the adaptive immune resistance gene (B7-H3 or CD47), and this immune classification system will facilitate HCC patient selection for ICI immunotherapy.

摘要

: 最近的研究表明,免疫检查点抑制剂 (ICI) 治疗在包括晚期肝细胞癌 (HCC) 在内的许多类型的晚期癌症中取得了成功。然而,ICI 治疗仅在一些 HCC 患者中是有益的,这表明在 HCC 中免疫反应是高度可变的。因此,了解 HCC 微环境中的免疫状态将有助于 ICI 免疫治疗,并指导患者选择治疗。在这项研究中,我们首先使用从癌症基因组图谱-肝肝细胞癌 (TCGA-LIHC) 数据库下载的数据分析了免疫调节基因的表达谱及其与 HCC 患者生存的关系,并发现 CD276 (B7-H3) 和 CD47 的高表达与低生存率显著相关。然后,我们通过 B7-H3 (或 CD47) 和 cd8 的联合表达,确定了 4 种不同存活的 hcc 免疫亚型。B7-H3low/CD8high 或 CD47low/CD8low 患者生存最好,而 B7-H3high/CD8low 或 CD47high/CD8low 患者生存最差。在来自华南的另外 72 例 HCC 患者中验证了 4 种免疫亚型。总之,我们的研究结果表明,HCC 患者的预后与 T 细胞浸润 (CD8 表达) 和适应性免疫抵抗基因 (B7-H3 或 CD47) 的表达的免疫表型相关,这种免疫分类系统将有助于 ICI 免疫治疗的 HCC 患者选择。

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