ARID1A Downregulation Predicts High PD-L1 Expression and Worse Clinical Outcome in Patients With Gallbladder Cancer.
ARID1A Downregulation Predicts High PD-L1 Expression and Worse Clinical Outcome in Patients With Gallbladder Cancer.
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ARID1A 下调可预测胆囊癌患者的高 PD-L1 表达和更差的临床结果
DOI：
10.3389/fonc.2022.787897
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发表时间：
2022
影响因子：
4.7
通讯作者：
Liu H
中科院分区：
文献类型：
--
作者：
Nan L;Wang C;Wang J;Zhang S;Bo X;Wang Y;Liu H
最近的研究证实富含AT的相互作用结构域蛋白1A（ARID 1A）在肿瘤发生中起关键作用，但其在胆囊癌（GBC）中的作用尚不清楚。本回顾性研究共招募了224名来自中山医院的患者。收集患者的临床病理学和基线特征。进行生物信息学分析以揭示基因和信号通路的变化，并通过免疫组织化学染色测量ARID 1A和PD-L1表达以及PD 1+肿瘤浸润淋巴细胞（TIL）的数量。ARID 1A表达与GBC患者的总生存率呈负相关，多变量分析将ARID 1A确定为总生存率的独立预后因素。热图和基因集富集分析表明，细胞毒性T淋巴细胞特征和免疫相关信号传导途径在ARID 1A低肿瘤中下调。随后的免疫组化染色证实，ARID 1A表达与肿瘤微环境中的PD-L1表达和PD 1 + TILs呈负相关。Kaplan-Meier分析表明，ARID 1A高表达结合PD-L1低表达或PD 1 + TIL低计数与GBC患者的最佳预后相关。ARID 1A失活可能导致GBC患者的预后更差，可能是通过PD 1/PD-L1途径介导免疫逃避。
Recent studies have confirmed that AT-rich interactive domain-containing protein 1A (ARID1A) plays a critical role in tumorigenesis, but its role in gallbladder cancer (GBC) remains unclear. In total, 224 patients from Zhongshan Hospital were recruited for this retrospective study. The clinicopathological and baseline characteristics of the patients were collected. Bioinformatics analysis was performed to reveal variations in genes and signaling pathways, and ARID1A and PD-L1 expression and the number of PD1+ tumor-infiltrating lymphocytes (TILs) were measured by immunohistochemical staining. ARID1A expression was negatively correlated with overall survival in patients with GBC, and multivariate analysis identified ARID1A as an independent prognostic factor for overall survival. A heatmap and gene set enrichment analysis suggested that cytotoxic T lymphocyte signatures and immune-related signaling pathways were downregulated in ARID1A low tumors. Subsequent immunohistochemical staining confirmed that ARID1A expression was negatively correlated with PD-L1 expression and PD1+ TILs in the tumor microenvironment. The Kaplan–Meier analysis suggested that high ARID1A expression combined with low PD-L1 expression or low PD1+ TIL counts is associated with the best prognosis in patients with GBC. ARID1A inactivation can lead to a worse prognosis in patients with GBC, potentially by mediating immune evasion through the PD1/PD-L1 pathway.