Journal of Gastric Cancer

The Korean Gastric Cancer Association (대한위암학회)
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Clinical Significance of CLDN18.2 Expression in Metastatic Diffuse-Type Gastric Cancer

  • Kim, Seo Ree (Division of Medical Oncology, Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Shin, Kabsoo (Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Park, Jae Myung (Department of Gastric Cancer Centre, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Lee, Han Hong (Department of Gastric Cancer Centre, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Song, Kyo Yong (Department of Gastric Cancer Centre, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Lee, Sung Hak (Department of Gastric Cancer Centre, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Kim, Bohyun (Department of Gastric Cancer Centre, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Kim, Sang-Yeob (Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Seo, Junyoung (Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim, Jeong-Oh (Cancer Research Institute, College of Medicine, The Catholic University of Korea) ;
  • Roh, Sang-Young (Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Kim, In-Ho (Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
  • Received : 2020.06.16
  • Accepted : 2020.11.30
  • Published : 2020.12.31
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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.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2018R1C1B6008724).

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