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Stratifying hepatocellular carcinoma based on immunophenotypes for immunotherapy response and prognosis.

作者信息

Liu Yunpeng, Ji Hongchen, Wu Li-Hong, Wang Xiang-Xu, Yang Yue, Zhang Qiong, Zhang Hong-Mei

机构信息

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.

出版信息

Mol Ther Oncol. 2024 Oct 5;32(4):200890. doi: 10.1016/j.omton.2024.200890. eCollection 2024 Dec 19.


DOI:10.1016/j.omton.2024.200890
PMID:39498358
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11532917/
Abstract

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.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac9f/11532917/19806590b56f/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac9f/11532917/19806590b56f/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac9f/11532917/19806590b56f/gr8.jpg

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引用本文的文献

[1]
Immunity revealed: Stratifying hepatocellular carcinoma for precision immunotherapy.

Mol Ther Oncol. 2025-2-4

本文引用的文献

[1]
Prognostic Significance of the Royal Marsden Hospital (RMH) Score in Patients with Cancer: A Systematic Review and Meta-Analysis.

Cancers (Basel). 2024-5-11

[2]
Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.

CA Cancer J Clin. 2024

[3]
Multicentre phase II trial of cabozantinib in patients with hepatocellular carcinoma after immune checkpoint inhibitor treatment.

J Hepatol. 2024-8

[4]
Cancer biomarkers: Emerging trends and clinical implications for personalized treatment.

Cell. 2024-3-28

[5]
Regulatory T cell-mediated immunosuppression orchestrated by cancer: towards an immuno-genomic paradigm for precision medicine.

Nat Rev Clin Oncol. 2024-5

[6]
Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma.

Ann Oncol. 2024-5

[7]
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Cancer Cell. 2024-2-12

[8]
Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma.

NEJM Evid. 2022-8

[9]
Immunotherapy and transplantation for hepatocellular carcinoma.

J Hepatol. 2024-5

[10]
Biomarkers for immunotherapy of hepatocellular carcinoma.

Nat Rev Clin Oncol. 2023-11

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