The Third Department of Hepatobiliary Surgery and Organ Transplant Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
The Third Department of Hepatobiliary Surgery and Organ Transplant Center, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China.
Front Immunol. 2021 Jul 15;12:676922. doi: 10.3389/fimmu.2021.676922. eCollection 2021.
Immune checkpoint inhibitors(ICIs) that activate tumor-specific immune responses bring new hope for the treatment of hepatocellular carcinoma(HCC). However, there are still some problems, such as uncertain curative effects and low objective response rates, which limit the curative effect of immunotherapy. Therefore, it is an urgent problem to guide the use of ICIs in HCC based on molecular typing. We downloaded the The Cancer Genome Atlas-Liver hepatocellular carcinoma(TCGA-LIHC) and Mongolian-LIHC cohort. Unsupervised clustering was applied to the highly variable data regarding expression of DNA damage repair(DDR). The CIBERSORT was used to evaluate the proportions of immune cells. The connectivity map(CMap) and pRRophetic algorithms were used to predict the drug sensitivity. There were significant differences in DDR molecular subclasses in HCC(DDR1 and DDR2), and DDR1 patients had low expression of DDR-related genes, while DDR2 patients had high expression of DDR-related genes. Of the patients who received traditional treatment, DDR2 patients had significantly worse overall survival(OS) than DDR1 patients. In contrast, of the patients who received ICIs, DDR2 patients had significantly prolonged OS compared with DDR1 patients. Of the patients who received traditional treatment, patients with high DDR scores had worse OS than those with low DDR scores. However, the survival of patients with high DDR scores after receiving ICIs was significantly higher than that of patients with low DDR scores. The DDR scores of patients in the DDR2 group were significantly higher than those of patients in the DDR1 group. The tumor microenvironment(TME) of DDR2 patients was highly infiltrated by activated immune cells, immune checkpoint molecules and proinflammatory molecules and antigen presentation-related molecules. In this study, HCC patients were divided into the DDR1 and DDR2 group. Moreover, DDR status may serve as a potential biomarker to predict opposite clinical prognosis immunotherapy and non-immunotherapy in HCC.
免疫检查点抑制剂（ICIs）激活肿瘤特异性免疫反应，为肝细胞癌（HCC）的治疗带来新的希望。然而，疗效不确定和客观缓解率低等问题仍然存在，限制了免疫治疗的疗效。因此，基于分子分型指导 HCC 中 ICI 的使用是一个亟待解决的问题。我们下载了 The Cancer Genome Atlas-Liver hepatocellular carcinoma（TCGA-LIHC）和 Mongolian-LIHC 队列。对 DNA 损伤修复（DDR）表达的高度变化数据应用无监督聚类。使用 CIBERSORT 评估免疫细胞的比例。使用 Connectivity Map（CMap）和 pRRophetic 算法预测药物敏感性。HCC（DDR1 和 DDR2）的 DDR 分子亚类存在显著差异，DDR1 患者 DDR 相关基因表达水平较低，而 DDR2 患者 DDR 相关基因表达水平较高。在接受传统治疗的患者中，DDR2 患者的总生存期（OS）明显差于 DDR1 患者。相反，在接受 ICI 治疗的患者中，DDR2 患者的 OS 明显长于 DDR1 患者。在接受传统治疗的患者中，DDR 评分高的患者的 OS 明显差于 DDR 评分低的患者。然而，接受 ICI 治疗后 DDR 评分高的患者的生存率明显高于 DDR 评分低的患者。DDR2 组患者的 DDR 评分明显高于 DDR1 组患者。DDR2 患者的肿瘤微环境（TME）中激活的免疫细胞、免疫检查点分子和促炎分子以及抗原呈递相关分子高度浸润。在这项研究中，HCC 患者被分为 DDR1 和 DDR2 组。此外，DDR 状态可能作为一种潜在的生物标志物，预测 HCC 中免疫治疗和非免疫治疗的相反临床预后。
