Scholarlink

Objective <p>This study aimed to clarify the clinical significance of ARID1A expression in gastric cancer (GC) and explore its mechanistic role in regulating PD-L1 expression during immunotherapy response.</p> Methods <p>A comprehensive analysis of ARID1A expression was conducted in 205 gastric adenocarcinoma specimens and 30 matched paracancerous tissues. ARID1A and PD-L1 expression profiles were assessed through immunohistochemical analysis. Functional studies using ARID1A-depleted GC cell lines were performed to uncover the underlying molecular mechanisms, with a particular focus on the PI3K/AKT signaling pathway. </p> Results <p>ARID1A deficiency was predominantly observed in GC tissues (42.4%) compared to paracancerous tissues (13.3%, <i>P</i> &lt; 0.01). This loss was significantly associated with aggressive clinicopathological features and reduced overall survival (median: 21.2 <i>vs</i>. 49.0&#xa0;months, <i>P</i> &lt; 0.001). Multivariate analysis identified ARID1A as an independent prognostic indicator. ARID1A status significantly influenced the efficacy of PD-1 inhibitors (<i>P</i> &lt; 0.01), with its loss predicting an enhanced therapeutic response. Mechanistically, ARID1A depletion promoted tumor aggressiveness and increased PD-L1 expression via activation of the PI3K/AKT pathway.</p> Conclusion <p>Our findings demonstrate that ARID1A deficiency, while linked to poor prognosis, paradoxically enhances sensitivity to immunotherapy in GC. The newly identified ARID1A-PI3K/AKT-PD-L1 axis represents a promising therapeutic target, highlighting the potential utility of PI3K/AKT inhibitors in treating ARID1A-deficient GC.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

The role and mechanism of ARID1A in immunotherapy of gastric cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月6日

查看全文
  • Wenting He,
  • Yue Chen,
  • Xue Yao,
  • Jun Wu,
  • Danxia Zhu,
  • Jian Wang,
  • Lu Jiang,
  • Yueping Shen,
  • Dachuan Zhang,
  • Jingting Jiang

摘要

Objective

This study aimed to clarify the clinical significance of ARID1A expression in gastric cancer (GC) and explore its mechanistic role in regulating PD-L1 expression during immunotherapy response.

Methods

A comprehensive analysis of ARID1A expression was conducted in 205 gastric adenocarcinoma specimens and 30 matched paracancerous tissues. ARID1A and PD-L1 expression profiles were assessed through immunohistochemical analysis. Functional studies using ARID1A-depleted GC cell lines were performed to uncover the underlying molecular mechanisms, with a particular focus on the PI3K/AKT signaling pathway.

Results

ARID1A deficiency was predominantly observed in GC tissues (42.4%) compared to paracancerous tissues (13.3%, P < 0.01). This loss was significantly associated with aggressive clinicopathological features and reduced overall survival (median: 21.2 vs. 49.0 months, P < 0.001). Multivariate analysis identified ARID1A as an independent prognostic indicator. ARID1A status significantly influenced the efficacy of PD-1 inhibitors (P < 0.01), with its loss predicting an enhanced therapeutic response. Mechanistically, ARID1A depletion promoted tumor aggressiveness and increased PD-L1 expression via activation of the PI3K/AKT pathway.

Conclusion

Our findings demonstrate that ARID1A deficiency, while linked to poor prognosis, paradoxically enhances sensitivity to immunotherapy in GC. The newly identified ARID1A-PI3K/AKT-PD-L1 axis represents a promising therapeutic target, highlighting the potential utility of PI3K/AKT inhibitors in treating ARID1A-deficient GC.