TY - JOUR
T1 - High proportion of potential candidates for immunotherapy in a chilean cohort of gastric cancer patients
T2 - Results of the FORCE1 study
AU - Cordova-Delgado, Miguel
AU - Pinto, Mauricio P.
AU - Retamal, Ignacio N.
AU - Muñoz-Medel, Matías
AU - Bravo, María Loreto
AU - Fernández, María F.
AU - Cisternas, Betzabé
AU - Mondaca, Sebastián
AU - Sanchez, César
AU - Galindo, Hector
AU - Nervi, Bruno
AU - Ibáñez, Carolina
AU - Acevedo, Francisco
AU - Madrid, Jorge
AU - Peña, José
AU - Koch, Erica
AU - Maturana, Maria José
AU - Romero, Diego
AU - de la Jara, Nathaly
AU - Torres, Javiera
AU - Espinoza, Manuel
AU - Balmaceda, Carlos
AU - Liao, Yuwei
AU - Li, Zhiguang
AU - Freire, Matías
AU - Gárate-Calderón, Valentina
AU - Cáceres, Javier
AU - Sepúlveda-Hermosilla, Gonzalo
AU - Lizana, Rodrigo
AU - Ramos, Liliana
AU - Artigas, Rocío
AU - Norero, Enrique
AU - Crovari, Fernando
AU - Armisén, Ricardo
AU - Corvalán, Alejandro H.
AU - Owen, Gareth I.
AU - Garrido, Marcelo
N1 - 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.
PY - 2019/9
Y1 - 2019/9
N2 - 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.
AB - 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.
KW - Cancer subtypes
KW - Gastric adenocarcinoma
KW - Gastric cancer
KW - Molecular
KW - Prognosis
KW - Survival
KW - Cancer subtypes
KW - Gastric adenocarcinoma
KW - Gastric cancer
KW - Molecular
KW - Prognosis
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=85072180621&partnerID=8YFLogxK
U2 - 10.3390/cancers11091275
DO - 10.3390/cancers11091275
M3 - Article
AN - SCOPUS:85072180621
SN - 2072-6694
VL - 11
JO - Cancers
JF - Cancers
IS - 9
M1 - 1275
ER -
