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...
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MDPI AG
2019-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/9/1275 |
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| author | Miguel Cordova-Delgado Mauricio P. Pinto Ignacio N. Retamal Matías Muñoz-Medel María Loreto Bravo María F. Fernández Betzabé Cisternas Sebastián Mondaca César Sanchez Hector Galindo Bruno Nervi Carolina Ibáñez Francisco Acevedo Jorge Madrid José Peña Erica Koch Maria José Maturana Diego Romero Nathaly de la Jara Javiera Torres Manuel Espinoza Carlos Balmaceda Yuwei Liao Zhiguang Li Matías Freire Valentina Gárate-Calderón Javier Cáceres Gonzalo Sepúlveda-Hermosilla Rodrigo Lizana Liliana Ramos Rocío Artigas Enrique Norero Fernando Crovari Ricardo Armisén Alejandro H. Corvalán Gareth I. Owen Marcelo Garrido |
| author_facet | Miguel Cordova-Delgado Mauricio P. Pinto Ignacio N. Retamal Matías Muñoz-Medel María Loreto Bravo María F. Fernández Betzabé Cisternas Sebastián Mondaca César Sanchez Hector Galindo Bruno Nervi Carolina Ibáñez Francisco Acevedo Jorge Madrid José Peña Erica Koch Maria José Maturana Diego Romero Nathaly de la Jara Javiera Torres Manuel Espinoza Carlos Balmaceda Yuwei Liao Zhiguang Li Matías Freire Valentina Gárate-Calderón Javier Cáceres Gonzalo Sepúlveda-Hermosilla Rodrigo Lizana Liliana Ramos Rocío Artigas Enrique Norero Fernando Crovari Ricardo Armisén Alejandro H. Corvalán Gareth I. Owen Marcelo Garrido |
| author_sort | Miguel Cordova-Delgado |
| collection | DOAJ |
| 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; <i>n</i> = 90) and next generation sequencing (NGS; <i>n</i> = 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, <i>TP53</i> and <i>PIK3CA</i> were the most frequently altered genes. However, NGS demonstrated the presence of <i>TP53</i>, <i>NRAS</i>, and <i>BRAF</i> 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. |
| first_indexed | 2024-03-12T11:05:11Z |
| format | Article |
| id | doaj.art-154366555e504be2a4fb8626cee526d4 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T11:05:11Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-154366555e504be2a4fb8626cee526d42023-09-02T04:01:57ZengMDPI AGCancers2072-66942019-08-01119127510.3390/cancers11091275cancers11091275High Proportion of Potential Candidates for Immunotherapy in a Chilean Cohort of Gastric Cancer Patients: Results of the FORCE1 StudyMiguel Cordova-Delgado0Mauricio P. Pinto1Ignacio N. Retamal2Matías Muñoz-Medel3María Loreto Bravo4María F. Fernández5Betzabé Cisternas6Sebastián Mondaca7César Sanchez8Hector Galindo9Bruno Nervi10Carolina Ibáñez11Francisco Acevedo12Jorge Madrid13José Peña14Erica Koch15Maria José Maturana16Diego Romero17Nathaly de la Jara18Javiera Torres19Manuel Espinoza20Carlos Balmaceda21Yuwei Liao22Zhiguang Li23Matías Freire24Valentina Gárate-Calderón25Javier Cáceres26Gonzalo Sepúlveda-Hermosilla27Rodrigo Lizana28Liliana Ramos29Rocío Artigas30Enrique Norero31Fernando Crovari32Ricardo Armisén33Alejandro H. Corvalán34Gareth I. Owen35Marcelo Garrido36Hematology & Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile (PUC), Santiago 8330032, ChileHematology & Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile (PUC), Santiago 8330032, ChileHematology & Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile (PUC), Santiago 8330032, ChileHematology & Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile (PUC), Santiago 8330032, ChileHematology & Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile (PUC), Santiago 8330032, ChileHematology & Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile (PUC), Santiago 8330032, ChileHematology & Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile (PUC), Santiago 8330032, ChileHematology & Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile (PUC), Santiago 8330032, ChileHematology & Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile (PUC), Santiago 8330032, ChileHematology & Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile (PUC), Santiago 8330032, ChileHematology & Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile (PUC), Santiago 8330032, ChileHematology & Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile (PUC), Santiago 8330032, ChileHematology & Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile (PUC), Santiago 8330032, ChileHematology & Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile (PUC), Santiago 8330032, ChileHematology & Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile (PUC), Santiago 8330032, ChileHematology & Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile (PUC), Santiago 8330032, ChileHematology & Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile (PUC), Santiago 8330032, ChileDepartment of Pathology, Faculty of Medicine, PUC, Santiago 8330023, ChileDepartment of Pathology, Faculty of Medicine, PUC, Santiago 8330023, ChileDepartment of Pathology, Faculty of Medicine, PUC, Santiago 8330023, ChileCentre of Clinical Research, Health Technology Assessment Unit, PUC, Santiago 8330032, ChileCentre of Clinical Research, Health Technology Assessment Unit, PUC, Santiago 8330032, ChileCenter of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, Liaoning, ChinaCenter of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, Liaoning, ChinaCenter of Excellence in Precision Medicine (CEMP), Obispo Espinoza Campos 2526, Macul, Santiago 7810305, ChileCenter of Excellence in Precision Medicine (CEMP), Obispo Espinoza Campos 2526, Macul, Santiago 7810305, ChileCenter of Excellence in Precision Medicine (CEMP), Obispo Espinoza Campos 2526, Macul, Santiago 7810305, ChileCenter of Excellence in Precision Medicine (CEMP), Obispo Espinoza Campos 2526, Macul, Santiago 7810305, ChileCenter of Excellence in Precision Medicine (CEMP), Obispo Espinoza Campos 2526, Macul, Santiago 7810305, ChileCenter of Excellence in Precision Medicine (CEMP), Obispo Espinoza Campos 2526, Macul, Santiago 7810305, ChileAdvanced Center for Chronic Diseases (ACCDiS), Core Biodata, Santiago 8330034, ChileDepartment of Gastrointestinal Surgery, PUC, Santiago 8330024, ChileDepartment of Gastrointestinal Surgery, PUC, Santiago 8330024, ChileCenter of Excellence in Precision Medicine (CEMP), Obispo Espinoza Campos 2526, Macul, Santiago 7810305, ChileHematology & Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile (PUC), Santiago 8330032, ChileHematology & Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile (PUC), Santiago 8330032, ChileHematology & Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile (PUC), Santiago 8330032, ChileGastric 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; <i>n</i> = 90) and next generation sequencing (NGS; <i>n</i> = 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, <i>TP53</i> and <i>PIK3CA</i> were the most frequently altered genes. However, NGS demonstrated the presence of <i>TP53</i>, <i>NRAS</i>, and <i>BRAF</i> 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.https://www.mdpi.com/2072-6694/11/9/1275gastric cancergastric adenocarcinomacancer subtypesprognosissurvivalmolecular |
| spellingShingle | Miguel Cordova-Delgado Mauricio P. Pinto Ignacio N. Retamal Matías Muñoz-Medel María Loreto Bravo María F. Fernández Betzabé Cisternas Sebastián Mondaca César Sanchez Hector Galindo Bruno Nervi Carolina Ibáñez Francisco Acevedo Jorge Madrid José Peña Erica Koch Maria José Maturana Diego Romero Nathaly de la Jara Javiera Torres Manuel Espinoza Carlos Balmaceda Yuwei Liao Zhiguang Li Matías Freire Valentina Gárate-Calderón Javier Cáceres Gonzalo Sepúlveda-Hermosilla Rodrigo Lizana Liliana Ramos Rocío Artigas Enrique Norero Fernando Crovari Ricardo Armisén Alejandro H. Corvalán Gareth I. Owen Marcelo Garrido High Proportion of Potential Candidates for Immunotherapy in a Chilean Cohort of Gastric Cancer Patients: Results of the FORCE1 Study Cancers gastric cancer gastric adenocarcinoma cancer subtypes prognosis survival molecular |
| 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 | gastric cancer gastric adenocarcinoma cancer subtypes prognosis survival molecular |
| url | https://www.mdpi.com/2072-6694/11/9/1275 |
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