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Updated: Nov 22, 2025
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Clinical Significance of CLDN18.2 Expression in Metastatic Diffuse-Type Gastric Cancer
Seo Ree Kim1, Kabsoo Shin2,3, Jae Myung Park3,4
1Division of Medical Oncology, Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Purpose:
Isoform 2 of tight junction protein claudin-18 (CLDN18.2) is a potential target for gastric cancer treatment. A treatment targeting CLDN18.2 has shown promising results in gastric cancer. We investigated the clinical significance of CLDN18.2 and other cell-adherens junction molecules (Rho GTPase-activating protein [RhoGAP] and E-cadherin) in metastatic diffuse-type gastric cancer (mDGC).
Materials And Methods:
We evaluated CLDN18.2, RhoGAP, and E-cadherin expression using two-plex immunofluorescence and quantitative data analysis of H-scores of 77 consecutive mDGC patients who received first-line platinum-based chemotherapy between March 2015 and February 2017.
Results:
CLDN18.2 and E-cadherin expression was significantly lower in patients with peritoneal metastasis (PM) than those without PM at the time of diagnosis (P=0.010 and 0.013, respectively), whereas it was significantly higher in patients who never developed PM from diagnosis to death than in those who did (P=0.001 and 0.003, respectively). Meanwhile, CLDN18.2 and E-cadherin expression levels were significantly higher in patients with bone metastasis than in those without bone metastasis (P=0.010 and 0.001, respectively). Moreover, we identified a positive correlation between the expression of CLDN18.2 and E-cadherin (P<0.001), RhoGAP and CLDN18.2 (P=0.004), and RhoGAP and E-cadherin (P=0.001). Conversely, CLDN18.2, RhoGAP, and E-cadherin expression was not associated with chemotherapy response and survival.
Conclusions:
CLDN18.2 expression was reduced in patients with PM but significantly intact in those with bone metastasis. Furthermore, CLDN18.2 expression was positively correlated with other adherens junction molecules, which is clinically associated with mDGC and PM pathogenesis.
Insights
Claudin-18.2 (CLDN18.2) expression is reduced in metastatic diffuse-type gastric cancer (mDGC) patients with peritoneal metastasis but intact in those with bone metastasis. CLDN18.2 correlates with other cell junction molecules, impacting mDGC and peritoneal metastasis pathogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Claudin-18.2 (CLDN18.2) is a potential therapeutic target in gastric cancer.
- Cell-adherens junction molecules play crucial roles in cancer progression.
Purpose of the Study:
- To investigate the clinical significance of CLDN18.2, Rho GTPase-activating protein (RhoGAP), and E-cadherin in metastatic diffuse-type gastric cancer (mDGC).
- To explore the association of these molecules with metastasis and treatment outcomes.
Main Methods:
- Immunofluorescence and quantitative H-score analysis were used to evaluate CLDN18.2, RhoGAP, and E-cadherin expression.
- The study included 77 mDGC patients receiving first-line platinum-based chemotherapy.
Main Results:
- CLDN18.2 and E-cadherin expression were lower in patients with peritoneal metastasis (PM) but higher in those with bone metastasis.
- Positive correlations were found between CLDN18.2, E-cadherin, and RhoGAP expression.
- Expression levels were not associated with chemotherapy response or survival.
Conclusions:
- CLDN18.2 expression is altered in mDGC based on metastatic site (peritoneal vs. bone).
- CLDN18.2 is positively correlated with E-cadherin and RhoGAP, suggesting a role in mDGC and PM pathogenesis.
