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High Proportion of Potential Candidates for Immunotherapy in a Chilean Cohort of Gastric Cancer Patients: Results of the FORCE1 Study
Gastric cancer (GC) is a heterogeneous disease. This heterogeneity applies not only to morphological and phenotypic features but also to geographical variations in incidence and mortality rates. As Chile has one of the highest mortality rates within South America, we sought to define a molecular pro...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770659/ https://www.ncbi.nlm.nih.gov/pubmed/31480291 http://dx.doi.org/10.3390/cancers11091275 |
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author | Cordova-Delgado, Miguel Pinto, Mauricio P. Retamal, Ignacio N. Muñoz-Medel, Matías Bravo, María Loreto Fernández, María F. Cisternas, Betzabé Mondaca, Sebastián Sanchez, César Galindo, Hector Nervi, Bruno Ibáñez, Carolina Acevedo, Francisco Madrid, Jorge Peña, José Koch, Erica Maturana, Maria José Romero, Diego de la Jara, Nathaly Torres, Javiera Espinoza, Manuel Balmaceda, Carlos Liao, Yuwei Li, Zhiguang Freire, Matías Gárate-Calderón, Valentina Cáceres, Javier Sepúlveda-Hermosilla, Gonzalo Lizana, Rodrigo Ramos, Liliana Artigas, Rocío Norero, Enrique Crovari, Fernando Armisén, Ricardo Corvalán, Alejandro H. Owen, Gareth I. Garrido, Marcelo |
author_facet | Cordova-Delgado, Miguel Pinto, Mauricio P. Retamal, Ignacio N. Muñoz-Medel, Matías Bravo, María Loreto Fernández, María F. Cisternas, Betzabé Mondaca, Sebastián Sanchez, César Galindo, Hector Nervi, Bruno Ibáñez, Carolina Acevedo, Francisco Madrid, Jorge Peña, José Koch, Erica Maturana, Maria José Romero, Diego de la Jara, Nathaly Torres, Javiera Espinoza, Manuel Balmaceda, Carlos Liao, Yuwei Li, Zhiguang Freire, Matías Gárate-Calderón, Valentina Cáceres, Javier Sepúlveda-Hermosilla, Gonzalo Lizana, Rodrigo Ramos, Liliana Artigas, Rocío Norero, Enrique Crovari, Fernando Armisén, Ricardo Corvalán, Alejandro H. Owen, Gareth I. Garrido, Marcelo |
author_sort | Cordova-Delgado, Miguel |
collection | PubMed |
description | Gastric cancer (GC) is a heterogeneous disease. This heterogeneity applies not only to morphological and phenotypic features but also to geographical variations in incidence and mortality rates. As Chile has one of the highest mortality rates within South America, we sought to define a molecular profile of Chilean GCs (ClinicalTrials.gov identifier: NCT03158571/(FORCE1)). Solid tumor samples and clinical data were obtained from 224 patients, with subsets analyzed by tissue microarray (TMA; n = 90) and next generation sequencing (NGS; n = 101). Most demographic and clinical data were in line with previous reports. TMA data indicated that 60% of patients displayed potentially actionable alterations. Furthermore, 20.5% were categorized as having a high tumor mutational burden, and 13% possessed micro-satellite instability (MSI). Results also confirmed previous studies reporting high Epstein-Barr virus (EBV) positivity (13%) in Chilean-derived GC samples suggesting a high proportion of patients could benefit from immunotherapy. As expected, TP53 and PIK3CA were the most frequently altered genes. However, NGS demonstrated the presence of TP53, NRAS, and BRAF variants previously unreported in current GC databases. Finally, using the Kendall method, we report a significant correlation between EBV+ status and programmed death ligand-1 (PDL1)+ and an inverse correlation between p53 mutational status and MSI. Our results suggest that in this Chilean cohort, a high proportion of patients are potential candidates for immunotherapy treatment. To the best of our knowledge, this study is the first in South America to assess the prevalence of actionable targets and to examine a molecular profile of GC patients. |
format | Online Article Text |
id | pubmed-6770659 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67706592019-10-30 High Proportion of Potential Candidates for Immunotherapy in a Chilean Cohort of Gastric Cancer Patients: Results of the FORCE1 Study Cordova-Delgado, Miguel Pinto, Mauricio P. Retamal, Ignacio N. Muñoz-Medel, Matías Bravo, María Loreto Fernández, María F. Cisternas, Betzabé Mondaca, Sebastián Sanchez, César Galindo, Hector Nervi, Bruno Ibáñez, Carolina Acevedo, Francisco Madrid, Jorge Peña, José Koch, Erica Maturana, Maria José Romero, Diego de la Jara, Nathaly Torres, Javiera Espinoza, Manuel Balmaceda, Carlos Liao, Yuwei Li, Zhiguang Freire, Matías Gárate-Calderón, Valentina Cáceres, Javier Sepúlveda-Hermosilla, Gonzalo Lizana, Rodrigo Ramos, Liliana Artigas, Rocío Norero, Enrique Crovari, Fernando Armisén, Ricardo Corvalán, Alejandro H. Owen, Gareth I. Garrido, Marcelo Cancers (Basel) Article Gastric cancer (GC) is a heterogeneous disease. This heterogeneity applies not only to morphological and phenotypic features but also to geographical variations in incidence and mortality rates. As Chile has one of the highest mortality rates within South America, we sought to define a molecular profile of Chilean GCs (ClinicalTrials.gov identifier: NCT03158571/(FORCE1)). Solid tumor samples and clinical data were obtained from 224 patients, with subsets analyzed by tissue microarray (TMA; n = 90) and next generation sequencing (NGS; n = 101). Most demographic and clinical data were in line with previous reports. TMA data indicated that 60% of patients displayed potentially actionable alterations. Furthermore, 20.5% were categorized as having a high tumor mutational burden, and 13% possessed micro-satellite instability (MSI). Results also confirmed previous studies reporting high Epstein-Barr virus (EBV) positivity (13%) in Chilean-derived GC samples suggesting a high proportion of patients could benefit from immunotherapy. As expected, TP53 and PIK3CA were the most frequently altered genes. However, NGS demonstrated the presence of TP53, NRAS, and BRAF variants previously unreported in current GC databases. Finally, using the Kendall method, we report a significant correlation between EBV+ status and programmed death ligand-1 (PDL1)+ and an inverse correlation between p53 mutational status and MSI. Our results suggest that in this Chilean cohort, a high proportion of patients are potential candidates for immunotherapy treatment. To the best of our knowledge, this study is the first in South America to assess the prevalence of actionable targets and to examine a molecular profile of GC patients. MDPI 2019-08-30 /pmc/articles/PMC6770659/ /pubmed/31480291 http://dx.doi.org/10.3390/cancers11091275 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Cordova-Delgado, Miguel Pinto, Mauricio P. Retamal, Ignacio N. Muñoz-Medel, Matías Bravo, María Loreto Fernández, María F. Cisternas, Betzabé Mondaca, Sebastián Sanchez, César Galindo, Hector Nervi, Bruno Ibáñez, Carolina Acevedo, Francisco Madrid, Jorge Peña, José Koch, Erica Maturana, Maria José Romero, Diego de la Jara, Nathaly Torres, Javiera Espinoza, Manuel Balmaceda, Carlos Liao, Yuwei Li, Zhiguang Freire, Matías Gárate-Calderón, Valentina Cáceres, Javier Sepúlveda-Hermosilla, Gonzalo Lizana, Rodrigo Ramos, Liliana Artigas, Rocío Norero, Enrique Crovari, Fernando Armisén, Ricardo Corvalán, Alejandro H. Owen, Gareth I. Garrido, Marcelo High Proportion of Potential Candidates for Immunotherapy in a Chilean Cohort of Gastric Cancer Patients: Results of the FORCE1 Study |
title | High Proportion of Potential Candidates for Immunotherapy in a Chilean Cohort of Gastric Cancer Patients: Results of the FORCE1 Study |
title_full | High Proportion of Potential Candidates for Immunotherapy in a Chilean Cohort of Gastric Cancer Patients: Results of the FORCE1 Study |
title_fullStr | High Proportion of Potential Candidates for Immunotherapy in a Chilean Cohort of Gastric Cancer Patients: Results of the FORCE1 Study |
title_full_unstemmed | High Proportion of Potential Candidates for Immunotherapy in a Chilean Cohort of Gastric Cancer Patients: Results of the FORCE1 Study |
title_short | High Proportion of Potential Candidates for Immunotherapy in a Chilean Cohort of Gastric Cancer Patients: Results of the FORCE1 Study |
title_sort | high proportion of potential candidates for immunotherapy in a chilean cohort of gastric cancer patients: results of the force1 study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770659/ https://www.ncbi.nlm.nih.gov/pubmed/31480291 http://dx.doi.org/10.3390/cancers11091275 |
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