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High Proportion of Potential Candidates for Immunotherapy in a Chilean Cohort of Gastric Cancer Patients: Results of the FORCE1 Study

1
Hematology & Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile (PUC), Santiago 8330032, Chile
2
Faculty of Chemical & Pharmaceutical Sciences, Universidad de Chile, Santiago 8380494, Chile
3
Department of Physiology, Faculty of Biological Sciences, PUC, Santiago 8331150, Chile
4
Faculty of Dentistry, Universidad de Los Andes, Santiago 7591538, Chile
5
Department of Pathology, Faculty of Medicine, PUC, Santiago 8330023, Chile
6
Advanced Center for Chronic Diseases (ACCDiS), Core Biodata, Santiago 8330034, Chile
7
Centre of Clinical Research, Health Technology Assessment Unit, PUC, Santiago 8330032, Chile
8
Department of Public Health, PUC, Santiago 8330032, Chile
9
Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, Liaoning, China
10
Center of Excellence in Precision Medicine (CEMP), Obispo Espinoza Campos 2526, Macul, Santiago 7810305, Chile
11
Department of Gastrointestinal Surgery, PUC, Santiago 8330024, Chile
12
Biomedical Research Consortium of Chile, Santiago 8331010, Chile
13
Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2019, 11(9), 1275; https://doi.org/10.3390/cancers11091275
Received: 2 August 2019 / Revised: 21 August 2019 / Accepted: 28 August 2019 / Published: 30 August 2019
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. View Full-Text
Keywords: gastric cancer; gastric adenocarcinoma; cancer subtypes; prognosis; survival; molecular gastric cancer; gastric adenocarcinoma; cancer subtypes; prognosis; survival; molecular
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Cordova-Delgado, M.; Pinto, M.P.; Retamal, I.N.; Muñoz-Medel, M.; Bravo, M.L.; Fernández, M.F.; Cisternas, B.; Mondaca, S.; Sanchez, C.; Galindo, H.; Nervi, B.; Ibáñez, C.; Acevedo, F.; Madrid, J.; Peña, J.; Koch, E.; Maturana, M.J.; Romero, D.; de la Jara, N.; Torres, J.; Espinoza, M.; Balmaceda, C.; Liao, Y.; Li, Z.; Freire, M.; Gárate-Calderón, V.; Cáceres, J.; Sepúlveda-Hermosilla, G.; Lizana, R.; Ramos, L.; Artigas, R.; Norero, E.; Crovari, F.; Armisén, R.; Corvalán, A.H.; Owen, G.I.; Garrido, M. High Proportion of Potential Candidates for Immunotherapy in a Chilean Cohort of Gastric Cancer Patients: Results of the FORCE1 Study. Cancers 2019, 11, 1275.

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