The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China.
Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, China.
J Cancer Res Clin Oncol. 2022 Jul;148(7):1583-1595. doi: 10.1007/s00432-022-03971-w. Epub 2022 Mar 16.
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).
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.
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.
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.
抑癌基因富含 AT 相互作用域 1A（ARID1A）和全身炎症反应（SIR）已被报道与免疫治疗的敏感性有关。本研究旨在探讨 ARID1A 表达与 SIR 的关系，并进一步阐明 ARID1A 表达在胃癌（GC）中的预后价值。
检测 272 例福尔马林固定石蜡包埋（FFPE）肿瘤组织中 ARID1A 的 mRNA 和蛋白表达。收集胃切除术前 1 周内 9 种全身炎症标志物的数据。采用单因素和多因素 COX 分析筛选 GC 的独立预测因子。
ARID1A 蛋白阴性表达与错配修复缺陷（dMMR）（p=0.033）、阳性程序性细胞死亡配体 1（PD-L1）（p=0.005）和低白蛋白水平（p=0.0064）相关。ARID1A mRNA 低表达常见于 E-钙黏蛋白异常（p=0.020）和血小板/淋巴细胞比值（PLR）较高的 GC（p=0.0391）。多因素 COX 分析显示，ARID1A 蛋白表达（p=0.023）、年龄（p=0.004）、T 分期（p=0.009）和 N 分期（p=0.009）是 GC 的独立预测因子。由独立预测因子建立的列线图可以准确评估 GC 患者的生存风险。
ARID1A 蛋白表达缺失与 GC 的 dMMR 亚型和 PD-L1 高表达有关。ARID1A 蛋白阴性和 mRNA 低表达与异常的全身炎症标志物有关。ARID1A 蛋白的表达在 GC 中具有重要的预后意义。
