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

<b>Background:</b> 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 G...

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Main Authors: Marina Alessandra Pereira, Marcus Fernando Kodama Pertille Ramos, Andre Roncon Dias, Leonardo Cardili, Renan Ribeiro e Ribeiro, Tiago Biachi de Castria, Bruno Zilberstein, Sergio Carlos Nahas, Ulysses Ribeiro, Evandro Sobroza de Mello
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Medical Sciences
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Online Access:https://www.mdpi.com/2076-3271/10/1/4
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author Marina Alessandra Pereira
Marcus Fernando Kodama Pertille Ramos
Andre Roncon Dias
Leonardo Cardili
Renan Ribeiro e Ribeiro
Tiago Biachi de Castria
Bruno Zilberstein
Sergio Carlos Nahas
Ulysses Ribeiro
Evandro Sobroza de Mello
author_facet Marina Alessandra Pereira
Marcus Fernando Kodama Pertille Ramos
Andre Roncon Dias
Leonardo Cardili
Renan Ribeiro e Ribeiro
Tiago Biachi de Castria
Bruno Zilberstein
Sergio Carlos Nahas
Ulysses Ribeiro
Evandro Sobroza de Mello
author_sort Marina Alessandra Pereira
collection DOAJ
description <b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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.
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spelling doaj.art-57c53f5e8ae44689a68513f56818d3992023-11-30T21:27:30ZengMDPI AGMedical Sciences2076-32712021-12-01101410.3390/medsci10010004RhoA, Claudin 18, and c-MET in Gastric Cancer: Clinicopathological Characteristics and Prognostic Significance in Curative Resected PatientsMarina Alessandra Pereira0Marcus Fernando Kodama Pertille Ramos1Andre Roncon Dias2Leonardo Cardili3Renan Ribeiro e Ribeiro4Tiago Biachi de Castria5Bruno Zilberstein6Sergio Carlos Nahas7Ulysses Ribeiro8Evandro Sobroza de Mello9Instituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246-000, BrazilInstituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246-000, BrazilInstituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246-000, BrazilInstituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246-000, BrazilInstituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246-000, BrazilInstituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246-000, BrazilInstituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246-000, BrazilInstituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246-000, BrazilInstituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246-000, BrazilInstituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246-000, Brazil<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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.https://www.mdpi.com/2076-3271/10/1/4gastric cancerclaudin 18Ras Homolog Family Member Ac-Mesenchymal–Epithelial Transitionimmunohistochemistry
spellingShingle Marina Alessandra Pereira
Marcus Fernando Kodama Pertille Ramos
Andre Roncon Dias
Leonardo Cardili
Renan Ribeiro e Ribeiro
Tiago Biachi de Castria
Bruno Zilberstein
Sergio Carlos Nahas
Ulysses Ribeiro
Evandro Sobroza de Mello
RhoA, Claudin 18, and c-MET in Gastric Cancer: Clinicopathological Characteristics and Prognostic Significance in Curative Resected Patients
Medical Sciences
gastric cancer
claudin 18
Ras Homolog Family Member A
c-Mesenchymal–Epithelial Transition
immunohistochemistry
title RhoA, Claudin 18, and c-MET in Gastric Cancer: Clinicopathological Characteristics and Prognostic Significance in Curative Resected Patients
title_full RhoA, Claudin 18, and c-MET in Gastric Cancer: Clinicopathological Characteristics and Prognostic Significance in Curative Resected Patients
title_fullStr RhoA, Claudin 18, and c-MET in Gastric Cancer: Clinicopathological Characteristics and Prognostic Significance in Curative Resected Patients
title_full_unstemmed RhoA, Claudin 18, and c-MET in Gastric Cancer: Clinicopathological Characteristics and Prognostic Significance in Curative Resected Patients
title_short RhoA, Claudin 18, and c-MET in Gastric Cancer: Clinicopathological Characteristics and Prognostic Significance in Curative Resected Patients
title_sort rhoa claudin 18 and c met in gastric cancer clinicopathological characteristics and prognostic significance in curative resected patients
topic gastric cancer
claudin 18
Ras Homolog Family Member A
c-Mesenchymal–Epithelial Transition
immunohistochemistry
url https://www.mdpi.com/2076-3271/10/1/4
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