Institute of Molecular Medicine, Medical College of Eastern Liaoning University, Dandong 118000, China.
Math Biosci Eng. 2022 May 16;19(7):7178-7200. doi: 10.3934/mbe.2022339.
Hepatocellular carcinoma is a highly malignant tumor and patients yield limited benefits from the existing treatments. The application of immune checkpoint inhibitors is promising but the results described in the literature are not favorable. It is therefore urgent to systematically analyze the immune microenvironment of HCC and screen the population best suited for the application of immune checkpoint inhibitors to provide a basis for clinical treatment. In this study, we collected The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC)-related data sets to evaluate the immune microenvironment and immune cell infiltration (ICI) in HCC. Three independent ICI subtypes showing significant differences in survival were identified. Further, TCGA-LIHC immunophenoscore (IPS) was used to identify the differentially expressed genes between high- and low-IPS in HCC, so as to identify the immune gene subtypes in HCC tumors. The ICI score model for HCC was constructed, whereby we divided HCC samples into high- and low-score groups based on the median ICI score. The differences between these groups in genomic mutation load and immunotherapy benefit in HCC were examined in detail to provide theoretical support for accurate immunotherapy strategy in HCC. Finally, four genes were screened, which could accurately predict the subtype based on the tumor immune infiltration score. The findings may provide a basis and simplify the process for screening clinical drugs suitable for relevant subgroups.
肝细胞癌是一种高度恶性的肿瘤，现有治疗方法对患者的获益有限。免疫检查点抑制剂的应用前景广阔，但文献中描述的结果并不理想。因此，迫切需要系统分析 HCC 的免疫微环境，并筛选最适合应用免疫检查点抑制剂的人群，为临床治疗提供依据。本研究收集了癌症基因组图谱肝脏肝癌（TCGA-LIHC）相关数据集，以评估 HCC 的免疫微环境和免疫细胞浸润（ICI）。确定了三种在生存方面存在显著差异的独立 ICI 亚型。进一步使用 TCGA-LIHC 免疫表型评分（IPS）来识别 HCC 中高 IPS 和低 IPS 之间的差异表达基因，以鉴定 HCC 肿瘤中的免疫基因亚型。构建了 HCC 的 ICI 评分模型，根据 ICI 评分的中位数将 HCC 样本分为高评分组和低评分组。详细研究了这些组在 HCC 基因组突变负荷和免疫治疗获益方面的差异，为 HCC 中准确的免疫治疗策略提供了理论支持。最后，筛选出了四个可以基于肿瘤免疫浸润评分准确预测亚型的基因。这些发现可能为筛选适合相关亚组的临床药物提供依据并简化其过程。
