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

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 correlati...

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Autores principales: Pereira, Marina Alessandra, Ramos, Marcus Fernando Kodama Pertille, Dias, Andre Roncon, Cardili, Leonardo, Ribeiro, Renan Ribeiro e, de Castria, Tiago Biachi, Zilberstein, Bruno, Nahas, Sergio Carlos, Ribeiro, Ulysses, de Mello, Evandro Sobroza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8788521/
https://www.ncbi.nlm.nih.gov/pubmed/35076580
http://dx.doi.org/10.3390/medsci10010004
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author Pereira, Marina Alessandra
Ramos, Marcus Fernando Kodama Pertille
Dias, Andre Roncon
Cardili, Leonardo
Ribeiro, Renan Ribeiro e
de Castria, Tiago Biachi
Zilberstein, Bruno
Nahas, Sergio Carlos
Ribeiro, Ulysses
de Mello, Evandro Sobroza
author_facet Pereira, Marina Alessandra
Ramos, Marcus Fernando Kodama Pertille
Dias, Andre Roncon
Cardili, Leonardo
Ribeiro, Renan Ribeiro e
de Castria, Tiago Biachi
Zilberstein, Bruno
Nahas, Sergio Carlos
Ribeiro, Ulysses
de Mello, Evandro Sobroza
author_sort Pereira, Marina Alessandra
collection PubMed
description 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.
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spelling pubmed-87885212022-01-26 RhoA, Claudin 18, and c-MET in Gastric Cancer: Clinicopathological Characteristics and Prognostic Significance in Curative Resected Patients Pereira, Marina Alessandra Ramos, Marcus Fernando Kodama Pertille Dias, Andre Roncon Cardili, Leonardo Ribeiro, Renan Ribeiro e de Castria, Tiago Biachi Zilberstein, Bruno Nahas, Sergio Carlos Ribeiro, Ulysses de Mello, Evandro Sobroza Med Sci (Basel) Article 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. MDPI 2021-12-29 /pmc/articles/PMC8788521/ /pubmed/35076580 http://dx.doi.org/10.3390/medsci10010004 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pereira, Marina Alessandra
Ramos, Marcus Fernando Kodama Pertille
Dias, Andre Roncon
Cardili, Leonardo
Ribeiro, Renan Ribeiro e
de Castria, Tiago Biachi
Zilberstein, Bruno
Nahas, Sergio Carlos
Ribeiro, Ulysses
de Mello, Evandro Sobroza
RhoA, Claudin 18, and c-MET in Gastric Cancer: Clinicopathological Characteristics and Prognostic Significance in Curative Resected Patients
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8788521/
https://www.ncbi.nlm.nih.gov/pubmed/35076580
http://dx.doi.org/10.3390/medsci10010004
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