CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题: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 失活可导致 GBC 患者预后更差,其可能通过 PD1/PD-L1 通路介导免疫逃逸。
近期研究证实,富含AT序列相互作用结构域蛋白1A(ARID1A)在肿瘤发生中发挥关键作用,但其在胆囊癌(GBC)中的作用尚不明确。
本回顾性研究纳入中山医院224例患者,收集其临床病理和基线特征。通过生物信息学分析揭示基因及信号通路变化,并采用免疫组化检测ARID1A和PD-L1表达,以及PD-1阳性TIL(肿瘤浸润淋巴细胞)数量。
GBC患者的ARID1A表达与总生存期相关,多变量分析确定ARID1A是总生存期的独立预后因素。热图和基因集富集分析提示,ARID1A低表达肿瘤中的细胞毒性T淋巴细胞特征及免疫相关信号通路下调。后续免疫组化证实,ARID1A表达与肿瘤微环境中PD-L1表达和PD-1阳性TIL数量呈负相关。Kaplan-Meier分析提示,ARID1A高表达且PD-L1低表达或PD-1阳性TIL较少的GBC患者预后最佳。
ARID1A失活可能通过PD-1/PD-L1通路介导免疫逃逸,导致GBC患者预后较差。
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.
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