Department of hepatobiliary and pancreatic surgery, Hainan General Hospital , Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, China.
Geriatrics center, Hainan General Hospital , Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, China.
Biomed Pharmacother. 2020 Jun;126:109903. doi: 10.1016/j.biopha.2020.109903. Epub 2020 Feb 26.
The significant response of immunotherapy is currently limited to a small number of patients, which has a high degree of selectivity. Therefore, distinguishing the immune subtypes of the tumor is necessary for patients who may benefit from immune checkpoint therapy. Clinical data and RNA expression data from The Cancer Genome Atlas (TCGA) and GENE EXPRESSION OMNIBUS (GEO) databases were used to study the relationship of immune regulatory pathways with immune subtypes, and the effects on the prognosis of hepatocellular carcinoma (HCC) patients. Eight immune checkpoint coding genes (ICGs) were obtained that closely related to prognosis. Adaptive immune pathway genes (CD8A, CD68, GZMB, and NOS2) show significant positive correlation with most of ICGs. Therefore, adaptive immune pathway genes may play a certain regulatory role in the expression of ICGs. Among the four immune subtypes, the group with low expression level of PD-L1, IDO1 and CTLA4, and high expression of CD8A had showed the best prognosis. The prognosis was the worst in the group with low expression of PD-L1, IDO1 and CTLA4, and showed low expression of CD8A. This research proposed a method to analyze the gene expression profile of immune checkpoints. The present method can be applied to identify the relationship between immune subtype of HCC and the prognosis, providing basis for gene immunotherapy in HCC patients.
免疫疗法的显著疗效目前仅限于少数具有高度选择性的患者。因此，区分肿瘤的免疫亚型对于可能受益于免疫检查点治疗的患者是必要的。本研究利用来自癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）的临床数据和 RNA 表达数据，研究了免疫调节途径与免疫亚型的关系及其对肝细胞癌（HCC）患者预后的影响。得到了 8 个与预后密切相关的免疫检查点编码基因（ICGs）。适应性免疫途径基因（CD8A、CD68、GZMB 和 NOS2）与大多数 ICGs 呈显著正相关。因此，适应性免疫途径基因可能在 ICGs 的表达中发挥一定的调节作用。在四个免疫亚型中，PD-L1、IDO1 和 CTLA4 表达水平低、CD8A 表达水平高的组显示出最好的预后。PD-L1、IDO1 和 CTLA4 表达水平低、CD8A 表达水平低的组预后最差。本研究提出了一种分析免疫检查点基因表达谱的方法。该方法可用于识别 HCC 的免疫亚型与预后之间的关系，为 HCC 患者的基因免疫治疗提供依据。
