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 Torres; Manuel 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

doi:10.3390/cancers11091275

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

Facultad de Odontología

Research output: Contribution to journal › Article › peer-review

17 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 language	English
Article number	1275
Journal	Cancers
Volume	11
Issue number	9
DOIs	https://doi.org/10.3390/cancers11091275
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cancers11091275

Cite this

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., ... Garrido, M. (2019). High proportion of potential candidates for immunotherapy in a chilean cohort of gastric cancer patients: Results of the FORCE1 study. Cancers, 11(9), Article 1275. https://doi.org/10.3390/cancers11091275

@article{ae3cec32558d46a7839a8b178c0a3aa2,

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

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.",

keywords = "Cancer subtypes, Gastric adenocarcinoma, Gastric cancer, Molecular, Prognosis, Survival, Cancer subtypes, Gastric adenocarcinoma, Gastric cancer, Molecular, Prognosis, Survival",

author = "Miguel Cordova-Delgado and Pinto, {Mauricio P.} and Retamal, {Ignacio N.} and Mat{\'i}as Mu{\~n}oz-Medel and Bravo, {Mar{\'i}a Loreto} and Fern{\'a}ndez, {Mar{\'i}a F.} and Betzab{\'e} Cisternas and Sebasti{\'a}n Mondaca and C{\'e}sar Sanchez and Hector Galindo and Bruno Nervi and Carolina Ib{\'a}{\~n}ez and Francisco Acevedo and Jorge Madrid and Jos{\'e} Pe{\~n}a and Erica Koch and Maturana, {Maria Jos{\'e}} and Diego Romero and {de la Jara}, Nathaly and Javiera Torres and Manuel Espinoza and Carlos Balmaceda and Yuwei Liao and Zhiguang Li and Mat{\'i}as Freire and Valentina G{\'a}rate-Calder{\'o}n and Javier C{\'a}ceres and Gonzalo Sep{\'u}lveda-Hermosilla and Rodrigo Lizana and Liliana Ramos and Roc{\'i}o Artigas and Enrique Norero and Fernando Crovari and Ricardo Armis{\'e}n and Corval{\'a}n, {Alejandro H.} and Owen, {Gareth I.} and Marcelo Garrido",

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{\textquoteright}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: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2019",

month = sep,

doi = "10.3390/cancers11091275",

language = "English",

volume = "11",

journal = "Cancers",

issn = "2072-6694",

publisher = "MDPI Multidisciplinary Digital Publishing Institute",

number = "9",

}

Cordova-Delgado, M, Pinto, MP, Retamal, IN, Muñoz-Medel, M, Bravo, ML, Fernández, MF, Cisternas, B, Mondaca, S, Sanchez, C, Galindo, H, Nervi, B, Ibáñez, C, Acevedo, F, Madrid, J, Peña, J, Koch, E, Maturana, MJ, 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, AH, Owen, GI & Garrido, M 2019, 'High proportion of potential candidates for immunotherapy in a chilean cohort of gastric cancer patients: Results of the FORCE1 study', Cancers, vol. 11, no. 9, 1275. https://doi.org/10.3390/cancers11091275

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 -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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