RhoA, Claudin 18, and c-MET in Gastric Cancer: Clinicopathological Characteristics and Prognostic Significance in Curative Resected Patients

Med Sci (Basel). 2021 Dec 29;10(1):4. doi: 10.3390/medsci10010004.

Abstract

Background: Recently, markers related to molecular classification were suggested as promising therapeutic targets for treatment and prediction of prognosis in gastric cancer (GC), including c-MET, RhoA, and Claudin-18 (CLDN18). This study aimed to investigate their expression in GC and its correlation with clinicopathological characteristics and survival. Methods: We retrospectively evaluated GC patients who underwent curative gastrectomy. c-MET, RhoA, and CLDN18 were analyzed through immunohistochemistry (IHC), and groups for analysis were determined according to the median values obtained for each marker. Results: Among the 349 GC evaluated, 180 (51.6%), 59 (16.9%), and 61 (17.5%) patients were completely negative for c-MET, RhoA, and CLDN18, respectively. Total gastrectomy, D1 lymphadenectomy, poorly differentiated histology, and greater inflammatory infiltrate were more frequent in the c-MET-negative group. Diffuse type, greater inflammatory infiltrate, and advanced pT and pTNM stage were associated with low-RhoA GC. The venous invasion was more frequent in the low-CLDN18 group. Furthermore, c-MET was positively correlated with RhoA and negatively with CLDN18. HER2 expression was associated with c-MET-positive and high-CLDN18 GC; and loss of E-cadherin expression in c-MET-negative and low-RhoA GC. c-MET-negative and Low-RhoA were significantly associated with worse disease-free survival. Conclusions: c-MET, RhoA, and CLD18 expression occurred frequently in GC. RhoA GC had distinct clinicopathological characteristics related to prognosis. c-MET and RhoA were associated with survival but were not independent predictors of prognosis.

Keywords: Ras Homolog Family Member A; c-Mesenchymal–Epithelial Transition; claudin 18; gastric cancer; immunohistochemistry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Cell Adhesion Molecules / metabolism
  • Claudins / metabolism
  • Humans
  • Prognosis
  • Proto-Oncogene Proteins c-met / metabolism*
  • Retrospective Studies
  • Stomach Neoplasms* / diagnosis
  • Stomach Neoplasms* / metabolism
  • Stomach Neoplasms* / surgery
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Biomarkers, Tumor
  • CLDN18 protein, human
  • Cell Adhesion Molecules
  • Claudins
  • RHOA protein, human
  • Proto-Oncogene Proteins c-met
  • rhoA GTP-Binding Protein