2. Academic Validation
  3. ARID1A deficiency promotes progression and potentiates therapeutic antitumour immunity in hepatitis B virus-related hepatocellular carcinoma

ARID1A deficiency promotes progression and potentiates therapeutic antitumour immunity in hepatitis B virus-related hepatocellular carcinoma

  • BMC Gastroenterol. 2024 Jan 2;24(1):11. doi: 10.1186/s12876-023-03059-w.
Tao Xing # 1 2,  Li Li # 1,  Xiaosong Rao # 3,  Jing Zhao 4,  Yiran Chen 5,  Gaoda Ju 1,  Yaping Xu 6,  Xuan Gao 6,  Guilan Dong 7,  Xuefeng Xia 6,  Yanfang Guan 6,  Lingling Zhang 8,  Zhenping Wen 9,  Jun Liang 10 11
Affiliations

Affiliations

  • 1 Departments of Oncology, Peking University International Hospital, 1 Life Park Road, Life Science Park of Zhongguancun, Changping, Beijing, 102206, China.
  • 2 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, No. 52, Fucheng Road, Haidian District, Beijing, 100142, China.
  • 3 HAINAN YILING Medical Industry Development Co.,Ldt, Qionghai, Hainan, 571442, China.
  • 4 Department of Pathology and Neuropathology, University Hospital Tübingen, Tübingen, 72074, Germany.
  • 5 Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, 350014, China.
  • 6 Geneplus-Beijing Institute, Beijing, 102206, China.
  • 7 Tangshan People's Hospital, Tangshan, Hebei, 063001, China.
  • 8 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, No. 52, Fucheng Road, Haidian District, Beijing, 100142, China. [email protected].
  • 9 Inner Mongolia Cancer Hospital, 42 Zhaowuda Road, Saihan District, Hohhot, Inner Mongolia, 010020, P. R. China. [email protected].
  • 10 Departments of Oncology, Peking University International Hospital, 1 Life Park Road, Life Science Park of Zhongguancun, Changping, Beijing, 102206, China. [email protected].
  • 11 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, No. 52, Fucheng Road, Haidian District, Beijing, 100142, China. [email protected].
  • # Contributed equally.
PMID: 38166741 DOI: 10.1186/s12876-023-03059-w
Abstract

Background: Exploring predictive biomarkers and therapeutic strategies of ICBs has become an urgent need in clinical practice. Increasing evidence has shown that ARID1A deficiency might play a critical role in sculpting tumor environments in various tumors and might be used as pan-cancer biomarkers for immunotherapy outcomes. The current study aims to explored the immune-modulating role of ARID1A deficiency in Hepatitis B virus (HBV) related hepatocellular carcinoma (HBV-HCC) and its potential immunotherapeutic implications.

Methods: In the current study, we performed a comprehensive analysis using bioinformatics approaches and pre-clinical experiments to evaluate the ARID1A regulatory role on the biological behavior, and immune landscape of Hepatitis B virus (HBV) related hepatocellular carcinoma (HBV-HCC). A total of 425 HBV-related hepatocellular carcinoma patients from TCGA-LIHC, AMC and CHCC-HBV cohort were enrolled in bioinformatics analysis. Immunohistochemical staining of HBV-HCC specimens and ARID1A deficiency cellular models were used to validate the results of the analysis.

Results: Our results have shown that ARID1A deficiency promoted tumor proliferation and metastasis. More importantly, ARID1A deficiency in HBV-HCC was associated with the higher TMB, elevated immune activity, and up-regulated expression of Immune Checkpoint Proteins, especially TIM-3 in HBV-HCC. Further, the expression of Galectin-9, which is the ligand of TIM-3, was elevated in the ARID1A knockout HBV positive cell line.

Conclusion: To conclude, we have shown that the ARID1A deficiency was correlated with more active immune signatures and higher expression of immune checkpoints in HBV-HCC. Additionally, the present study provides insights to explore the possibility of the predictive role of ARID1A in HBV-HCC patients responsive to immunotherapy.

Keywords

ARID1A; Hepatocellular carcinoma; Immunotherapy; TIM3; TMB.

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