Abstract
Background
The tumor suppressor gene AT-rich interactive domain 1A (ARID1A) and systemic inflammatory response (SIR) have been reported to be related to the sensitivity to immunotherapy. This study intended to explore the relationship between ARID1A expression and SIR, and to further elucidate the prognostic value of ARID1A expression in gastric cancer (GC).
Methods
The mRNA and protein expression of ARID1A were detected in 272 formalin-fixed paraffin-embedded (FFPE) tumor tissues. The data of nine systemic inflammation markers were collected 1 week before gastrectomy. Univariate and multivariate COX analysis were used to screen out independent predictors of GC.
Results
Negative expression of ARID1A protein was related to GC with deficient mismatch repair (dMMR) (p = 0.033), positive programmed cell death-ligand 1 (PD-L1) (p = 0.005) and lower albumin level (p = 0.0064). Low expression of ARID1A mRNA was common in GC with abnormal E-cadherin (p = 0.020) and a higher platelet/lymphocyte ratio (PLR) (p = 0.0391). Multivariate COX analysis showed that the expression of ARID1A protein (p = 0.023), age (p = 0.004), T stage (p = 0.009) and N stage (p = 0.009) were independent predictors of GC. The nomogram established by independent predictors can accurately evaluate the survival risk of patients with GC.
Conclusions
The loss of ARID1A protein expression was associated with the dMMR subtype and high expression of PD-L1 in GC. Negative ARID1A protein and low expression of mRNA were associated with aberrant systemic inflammatory markers. The expression of ARID1A protein had important prognostic significance in GC.
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Data availability
The data described in this manuscript are contained in published articles or available from the corresponding author upon reasonable request.
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Acknowledgements
The authors would like to thank all patients who participated in this study.
Funding
This work was funded by grants from National Natural Science Foundation of China (82073382) and the Distinguished Young Scholars of Jiangsu Province (BK20190001). The funding sources had no role in the study design, data collection, data analysis, data interpretation, or writing of this review. The funding sources have no involvement in study design; the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.
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XW: drafting the article; KC: revising it critically for important intellectual content; TS: the acquisition of data; QL: Visualization; XX: analysis and interpretation of data; HW: analysis and interpretation of data; LY: the acquisition of data; BL: supervision and final approval of the version to be submitted; JW: conceptualization and funding acquisition.
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This study was conducted in accordance with the code of ethics of the World Medical Association (Declaration of Helsinki) and approved by the Ethics Committee of Nan**g Drum Tower Hospital (No. 2016-196-01).
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Wang, X., Che, K., Shi, T. et al. Loss of ARID1A expression is associated with systemic inflammation markers and has important prognostic significance in gastric cancer. J Cancer Res Clin Oncol 148, 1583–1595 (2022). https://doi.org/10.1007/s00432-022-03971-w
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DOI: https://doi.org/10.1007/s00432-022-03971-w