J Gastric Cancer.  2020 Dec;20(4):408-420. 10.5230/jgc.2020.20.e33.

Clinical Significance of CLDN18.2 Expression in Metastatic Diffuse-Type Gastric Cancer

Affiliations
  • 1Division of Medical Oncology, Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
  • 2Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
  • 3Department of Gastric Cancer Centre, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
  • 4Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
  • 5Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
  • 6Department of Clinical Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
  • 7Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
  • 8Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  • 9Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  • 10Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea

Abstract

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.

Keyword

Gastric cancer; Claudin; Cadherins; Chemotherapy
Full Text Links
  • JGC
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
    DB Error: unknown error