High proportion of potential candidates for immunotherapy in a chilean cohort of gastric cancer patients: Results of the FORCE1 study

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 TorresManuel 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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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.

Original languageEnglish
Article number1275
JournalCancers
Volume11
Issue number9
DOIs
StatePublished - Sep 2019

Bibliographical note

Funding Information:
Funding: Sequencing analyses were funded by CEMP. The Pontificia Universidad Catolica de Chile wishes to acknowledge the support from the following grants: FONDECYT grants #1180173 (M.G.), #1180241 (G.I.O.), #1191928 (A.H.C.), BMRC 13CTI-21526-P6 (G.I.O., M.L.B.), CORFO 13IDL2-18608 (G.I.O., M.L.B.), IMII P09/016-F (G.I.O., M.L.B.) UC-PG14 (J.T., A.H.C.) & UC-IC 05/15 (M.G.); CONICYT-FONDAP-15130011 (G.I.O., A.H.C.). China’s National Natural Science Foundation (#. 81472637, 81672784, and 81872655). The first author (M.C.-D.) is a CONICYT doctoral scholarship recipient (#21150695).

Funding Information:
Sequencing analyses were funded by CEMP. The Pontificia Universidad Catolica de Chile wishes to acknowledge the support from the following grants: FONDECYT grants #1180173 (M.G.), #1180241 (G.I.O.), #1191928 (A.H.C.), BMRC 13CTI-21526-P6 (G.I.O., M.L.B.), CORFO 13IDL2-18608 (G.I.O., M.L.B.), IMII P09/016-F (G.I.O., M.L.B.) UC-PG14 (J.T., A.H.C.) & UC-IC 05/15 (M.G.); CONICYT-FONDAP-15130011 (G.I.O., A.H.C.). China?s National Natural Science Foundation (#. 81472637, 81672784, and 81872655). The first author (M.C.-D.) is a CONICYT doctoral scholarship recipient (#21150695).. Acknowledgments: We thank the participating patients of the study, and the University Hospital medical and nursing staff.

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Cancer subtypes
  • Gastric adenocarcinoma
  • Gastric cancer
  • Molecular
  • Prognosis
  • Survival

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