Xuan Wang1,2, Keying Che3, Tao Shi3, Qin Liu3, Xinyun Xu4, Hongyan Wu4, Lixia Yu3, Baorui Liu3, Jia Wei5. 1. The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China. 2. Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, China. 3. The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School and Clinical Cancer Institute of Nanjing University, No. 321, Zhongshan Road, Nanjing, 210008, China. 4. Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China. 5. The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School and Clinical Cancer Institute of Nanjing University, No. 321, Zhongshan Road, Nanjing, 210008, China. jiawei99@nju.edu.cn.
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.
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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