TY - JOUR
T1 - A molecular stratification of chilean gastric cancer patients with potential clinical applicability
AU - Pinto, Mauricio P.
AU - Córdova-Delgado, Miguel
AU - Retamal, Ignacio N.
AU - Muñoz-Medel, Matías
AU - Bravo, M. Loreto
AU - Durán, Doris
AU - Villanueva, Francisco
AU - Sanchez, César
AU - Acevedo, Francisco
AU - Mondaca, Sebastián
AU - Koch, Erica
AU - Ibañez, Carolina
AU - Galindo, Héctor
AU - Madrid, Jorge
AU - Nervi, Bruno
AU - Peña, José
AU - Torres, Javiera
AU - Owen, Gareth I.
AU - Corvalán, Alejandro H.
AU - Armisén, Ricardo
AU - Garrido, Marcelo
N1 - 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.
PY - 2020/7
Y1 - 2020/7
N2 - 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.
AB - 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.
KW - Epstein–Barr virus
KW - Gastric cancer
KW - Molecular classification
KW - Molecular subtypes
KW - Targeted therapy
KW - Epstein–Barr virus
KW - Gastric cancer
KW - Molecular classification
KW - Molecular subtypes
KW - Targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85088917444&partnerID=8YFLogxK
U2 - 10.3390/cancers12071863
DO - 10.3390/cancers12071863
M3 - Article
AN - SCOPUS:85088917444
SN - 2072-6694
VL - 12
SP - 1
EP - 14
JO - Cancers
JF - Cancers
IS - 7
M1 - 1863
ER -