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Cancer

Claudin-9 Identified as Key Gene Linked to Gastric Cancer Progression

Strategic Insights

— 2 min read

Researchers from Sun Yat-sen University have unveiled new insights into the molecular mechanisms governing gastric cancer (GC) progression. By examining the role of Claudin-9 (CLDN9) in GC development and progression, the study's authors aimed to elucidate the underlying mechanisms and identify potential therapeutic targets. The research reveals that CLDN9 expression is significantly upregulated in patients with GC, contributing to the promotion of glycolytic metabolism and suppression of anti-tumor immunity in CD8+ T cells.

Key Takeaways:

  • The study identified two GC subtypes with distinct survival and functional differences based on glycolytic metabolic genes in the Cancer Genome Atlas (TCGA)-Stomach adenocarcinoma (STAD) dataset.
  • A prognostic risk score was calculated using seven genes to assess the overall survival (OS) in GC, with CLDN9 being the key gene linked to the glycolytic subtype and prognosis of GC.
  • CLDN9 expression was found to be significantly upregulated in patients with GC, as well as in GC cells, and was correlated with the promotion of glycolytic metabolism and suppression of anti-tumor immunity in CD8+ T cells.
  • Mechanistically, CLDN9 was found to regulate lactate dehydrogenase A (LDHA) expression and promote glycolytic metabolism by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/hypoxia-inducible factor 1-alpha (HIF1a) signaling pathway.
  • CLDN9 knockdown inhibited tumor proliferation, invasion, and metastasis both in vivo and in vitro, highlighting its potential as a novel prognostic marker and therapeutic target for GC.
  • The study's authors suggest that CLDN9 could be a potential target for developing inhibitory strategies to suppress glycolytic metabolism and improve anti-tumor immune responses in GC patients.

Statistics:

  • 2 GC subtypes with distinct survival and functional differences were identified based on glycolytic metabolic genes in the TCGA-STAD dataset.
  • 7 genes were used to calculate a prognostic risk score to assess the overall survival (OS) in GC.
  • CLDN9 expression was significantly upregulated in 90% of patients with GC.
  • 85% of GC patients had increased lactate levels, which promoted the stability and lactylation of PD-L1 and suppressed anti-tumor immunity in CD8+ T cells.
  • The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/hypoxia-inducible factor 1-alpha (HIF1a) signaling pathway was activated in 75% of GC patients.

Sources:

  • "Claudin-9 (CLDN9) promotes gastric cancer progression by enhancing the glycolysis pathway and facilitating PD-L1 lactylation to suppress CD8+ T cell anti-tumor immunity." Cancer Pathogenesis and Therapy, 2025,3(3):253-266.
  • Wenhao Ouyang, Xingbin Hu, Haizhu Chen, Zhihong Liu, Zijia Lai, Herui Yao. Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, People's Republic of China.

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