Clinical implication of CLDN18, RhoGAP, and E-cadherin in gastric signet ring cell carcinoma

Background Signet ring cell carcinoma (SRCC), a subtype of gastric cancer (GC), has specific epidemiology and oncogenesis, and has poor prognosis; it still has the highest number of unmet medical needs. Cytoskeletal rearrangement and disruption of cell integrity play crucial roles in SRCC pathogenesis. Recently, many studies have been conducted on molecular alterations in SRCC; with the clarification of the clinical significance of the CLDN-ARHGAP fusion gene, a large clinical trial is underway. Herein, we examined the influence of CLDN, RhoGAP, and E-cadherin on SRCC prognosis. Methods We reviewed advanced 663 GC patients who received palliative chemotherapy. Of these, 135 patients (20.4%) were SRCC. Multiplexed immunofluorescence was performed on the tissue samples using antibodies against CLDN18, RhoGAP, and E-cadherin. Positivty was defined as the median value of H-score. Results Overall, 85 (63%) of 135 SRCC patients, were analysed based on tissue availability. Median age at GC diagnosis was 52.5 (range 20-77) years; the female-to-male ratio was 1.2. CLDN 18 showed a strong positive correlation with E-cadherin (r = 0.705, P Conclusions The correlations among CLDN18, RhoGAP, and E-cadherin may be associated with the discohesive oncogenesis seen in SRCC. We propose that these discohesive factors may be associated with prognosis of metastatic SRCC. Further functional studies are needed to clarify the role of these molecules. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.