Evidence map›Paper›PMID 40768000›Full record

ArticleClinical and experimental medicine2025

The role and mechanism of ARID1A in immunotherapy of gastric cancer.

Wenting He, Yue Chen, Xue Yao, Jun Wu, Danxia Zhu, Jian Wang, Lu Jiang, Yueping Shen, Dachuan Zhang, Jingting Jiang

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Article in Clinical and experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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10 authors.

Wenting He *Department of Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, 213003, Jiangsu Province, China.
Yue Chen *Department of Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, 213003, Jiangsu Province, China.
Xue Yao *Department of Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, 213003, Jiangsu Province, China.
Jun WuDepartment of Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, 213003, Jiangsu Province, China.
Danxia ZhuDepartment of Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, 213003, Jiangsu Province, China.
Jian WangDepartment of Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, 213003, Jiangsu Province, China.
Lu JiangDepartment of Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, 213003, Jiangsu Province, China.
Yueping ShenDepartment of Epidemiology and Biostatistics, School of Public Health, Medical College of Soochow University, 199 Renai Road, Suzhou, 215123, P. R. China.
Dachuan ZhangDepartment of Pathology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, 213003, Jiangsu Province, China. zhangdachuan@suda.edu.cn.
Jingting JiangDepartment of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, China. jiangjingting@suda.edu.cn.

Funding

2023 Changzhou Health Commission Science and Technology Project QY202301Changzhou Sci & Tech Program CJ20220064, CJ20243007Science and Technology Project of Changzhou Health Commission ZD202428Top Talent of Changzhou The 14th Five-Year Plan High-level Health Personnel Training Project 2022260Youth Talent Science and Technology Project of Changzhou Health Commission QN202434
6 · The paper itself

Abstract

objectiveThis study aimed to clarify the clinical significance of ARID1A expression in gastric cancer (GC) and explore its mechanistic role in regulating PD-L1 expression during immunotherapy response.

methodsA comprehensive analysis of ARID1A expression was conducted in 205 gastric adenocarcinoma specimens and 30 matched paracancerous tissues. ARID1A and PD-L1 expression profiles were assessed through immunohistochemical analysis. Functional studies using ARID1A-depleted GC cell lines were performed to uncover the underlying molecular mechanisms, with a particular focus on the PI3K/AKT signaling pathway.

resultsARID1A deficiency was predominantly observed in GC tissues (42.4%) compared to paracancerous tissues (13.3%, P < 0.01). This loss was significantly associated with aggressive clinicopathological features and reduced overall survival (median: 21.2 vs. 49.0 months, P < 0.001). Multivariate analysis identified ARID1A as an independent prognostic indicator. ARID1A status significantly influenced the efficacy of PD-1 inhibitors (P < 0.01), with its loss predicting an enhanced therapeutic response. Mechanistically, ARID1A depletion promoted tumor aggressiveness and increased PD-L1 expression via activation of the PI3K/AKT pathway.

conclusionOur findings demonstrate that ARID1A deficiency, while linked to poor prognosis, paradoxically enhances sensitivity to immunotherapy in GC. The newly identified ARID1A-PI3K/AKT-PD-L1 axis represents a promising therapeutic target, highlighting the potential utility of PI3K/AKT inhibitors in treating ARID1A-deficient GC.

Indexed as

DNA-Binding ProteinsImmunotherapyStomach NeoplasmsTranscription FactorsAdultAgedB7-H1 AntigenCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMaleMiddle AgedPhosphatidylinositol 3-KinasesPrognosisProto-Oncogene Proteins c-aktARID1A protein, humanB7-H1 AntigenCD274 protein, humanDNA-Binding ProteinsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktTranscription FactorsARID1AGastric cancerImmunotherapyPD-L1PI3K/AKT Pathway

Identifiers

PMID40768000
PMCPMC12328504

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.