Liu Yunpeng, Ji Hongchen, Wu Li-Hong, Wang Xiang-Xu, Yang Yue, Zhang Qiong, Zhang Hong-Mei
Department of Clinical Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Department of Gastroenterology, Xijing 986 Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Mol Ther Oncol. 2024 Oct 5;32(4):200890. doi: 10.1016/j.omton.2024.200890. eCollection 2024 Dec 19.
Immunotherapy has transformed the management of hepatocellular carcinoma (HCC), but effectiveness varies among patients. This study aimed to identify biomarkers and HCC subtypes responsive to immunotherapy. Patients were classified into Immunity-High (Immunity-H) and Immunity-Low (Immunity-L) subtypes using ssGSEA scores. Prognostic genes were identified through Cox regression, and immune cell infiltration was quantified with TIMER 2.0. Brother of CDO (BOC) expression, analyzed via immunohistochemistry, correlated with immunotherapy responses. Flow cytometry assessed immune cell infiltration relative to BOC levels, while CCK-8 and transwell assays evaluated BOC overexpression's effects on cell proliferation and invasiveness. Clinically, immunity-H patients had better survival outcomes. Three hub genes-BOC, V-Set and Transmembrane Domain Containing 1 (VSTM1), and PRDM12-were identified as significantly associated with prognosis. Among these, BOC and VSTM1 demonstrated positive correlations with immune cell infiltration. Elevated expression of BOC was found to be predictive of favorable responses to immunotherapy and was associated with enhanced infiltration of T cells, dendritic cells, and B cells in the tumor microenvironment. Conversely, BOC overexpression in liver cancer cell lines led to decreased cell proliferation and invasiveness. This study underscores the prognostic significance of HCC subtypes defined by immunogenomic profiles and identifies BOC as a potential biomarker for immunotherapy selection and outcome prediction.
免疫疗法已经改变了肝细胞癌（HCC）的治疗方式，但患者之间的疗效存在差异。本研究旨在识别对免疫疗法有反应的生物标志物和HCC亚型。使用单样本基因集富集分析（ssGSEA）分数将患者分为免疫高（Immunity-H）和免疫低（Immunity-L）亚型。通过Cox回归确定预后基因，并用TIMER 2.0对免疫细胞浸润进行定量。通过免疫组织化学分析的CDO兄弟（BOC）表达与免疫疗法反应相关。流式细胞术评估相对于BOC水平的免疫细胞浸润，而CCK-8和Transwell实验评估BOC过表达对细胞增殖和侵袭性的影响。临床上，免疫高的患者有更好的生存结果。确定了三个关键基因——BOC、含V-set和跨膜结构域1（VSTM1）以及PRDM12——与预后显著相关。其中，BOC和VSTM1与免疫细胞浸润呈正相关。发现BOC表达升高可预测对免疫疗法的良好反应，并与肿瘤微环境中T细胞、树突状细胞和B细胞浸润增加有关。相反，肝癌细胞系中BOC过表达导致细胞增殖和侵袭性降低。本研究强调了由免疫基因组图谱定义的HCC亚型的预后意义，并确定BOC作为免疫疗法选择和结果预测的潜在生物标志物。
