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.
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