A molecular stratification of chilean gastric cancer patients with potential clinical applicability

Mauricio P. Pinto, Miguel Córdova-Delgado, Ignacio N. Retamal, Matías Muñoz-Medel, M. Loreto Bravo, Doris Durán, Francisco Villanueva, César Sanchez, Francisco Acevedo, Sebastián Mondaca, Erica Koch, Carolina Ibañez, Héctor Galindo, Jorge Madrid, Bruno Nervi, José Peña, Javiera Torres, Gareth I. Owen, Alejandro H. Corvalán, Ricardo ArmisénMarcelo Garrido*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Gastric cancer (GC) is a complex and heterogeneous disease. In recent decades, The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) defined GC molecular subtypes. Unfortunately, these systems require high-cost and complex techniques and consequently their impact in the clinic has remained limited. Additionally, most of these studies are based on European, Asian, or North American GC cohorts. Herein, we report a molecular classification of Chilean GC patients into five subtypes, based on immunohistochemical (IHC) and in situ hybridization (ISH) methods. These were Epstein–Barr virus positive (EBV+), mismatch repair-deficient (MMR-D), epithelial to mesenchymal transition (EMT)-like, and accumulated (p53+) or undetected p53 (p53−). Given its lower costs this system has the potential for clinical applicability. Our results confirm relevant molecular alterations previously reported by TCGA and ACRG. We confirm EBV+ and MMR-D patients had the best prognosis and could be candidates for immunotherapy. Conversely, EMT-like displayed the poorest prognosis; our data suggest FGFR2 or KRAS could serve as potential actionable targets for these patients. Finally, we propose a low-cost step-by-step stratification system for GC patients. To the best of our knowledge, this is the first Latin American report on a molecular classification for GC. Pending further validation, this stratification system could be implemented into the routine clinic.

Original languageEnglish
Article number1863
Pages (from-to)1-14
Number of pages14
JournalCancers
Volume12
Issue number7
DOIs
StatePublished - Jul 2020

Bibliographical note

Funding Information:
This research was funded by FONDECYT, grant number 1180173. MC-D is a CONICYT doctoral scholarship recipient (#21150695).

Funding Information:
Funding: This research was funded by FONDECYT, grant number 1180173. MC-D is a CONICYT doctoral scholarship recipient (#21150695).

Funding Information:
Conflicts of Interest: BN is an advisor for Roche; JM is a consultant for Boehringer-Ingelheim and provides expert testimony to Roche; CS receives research funding from Roche and Novartis, and provides expert testimony for Pfizer and have received travel or accommodations, or expenses from Novartis and Pfizer; SM is a consultant for Foundation Medicine; EK participates at the speakers’ bureau for Novartis and have received travel support from Pfizer, Novartis and Roche Pharma; MG is an advisor for Merck Sharp & Dohme and Novartis, participates at the speakers’ bureau for Bristol-Myers & Squibb and Bayer. Also receives research funding from Bristol-Myers & Squibb (Inst) and Novartis (Inst). Also, has received travel accommodations and expenses from Roche. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Epstein–Barr virus
  • Gastric cancer
  • Molecular classification
  • Molecular subtypes
  • Targeted therapy

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