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

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dc.coverageDOI: 10.3390/cancers11091275
dc.creatorCordova-Delgado, Miguel
dc.creatorPinto, Mauricio P.
dc.creatorRetamal, Ignacio N.
dc.creatorMuñoz-Medel, Matías
dc.creatorBravo, María Loreto
dc.creatorFernández, María F.
dc.creatorCisternas, Betzabé
dc.creatorMondaca, Sebastián
dc.creatorSanchez, César
dc.creatorGalindo, Hector
dc.creatorNervi, Bruno
dc.creatorIbáñez, Carolina
dc.creatorAcevedo, Francisco
dc.creatorMadrid, Jorge
dc.creatorPeña, José
dc.creatorKoch, Erica
dc.creatorMaturana, Maria José
dc.creatorRomero, Diego
dc.creatorde la Jara, Nathaly
dc.creatorTorres, Javiera
dc.creatorEspinoza, Manuel
dc.creatorBalmaceda, Carlos
dc.creatorLiao, Yuwei
dc.creatorLi, Zhiguang
dc.creatorFreire, Matías
dc.creatorGárate-Calderón, Valentina
dc.creatorCáceres, Javier
dc.creatorSepúlveda-Hermosilla, Gonzalo
dc.creatorLizana, Rodrigo
dc.creatorRamos, Liliana
dc.creatorArtigas, Rocío
dc.creatorNorero, Enrique
dc.creatorCrovari, Fernando
dc.creatorArmisén, Ricardo
dc.creatorCorvalán, Alejandro H.
dc.creatorOwen, Gareth I.
dc.creatorGarrido, Marcelo
dc.date2019
dc.date.accessioned2025-11-18T19:54:23Z
dc.date.available2025-11-18T19:54:23Z
dc.description<p>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.</p>eng
dc.descriptionGastric 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.spa
dc.identifierhttps://investigadores.uandes.cl/en/publications/ae3cec32-558d-46a7-839a-8b178c0a3aa2
dc.identifier.urihttps://repositorio.uandes.cl/handle/uandes/58727
dc.languageeng
dc.rightsinfo:eu-repo/semantics/openAccess
dc.sourcevol.11 (2019) nr.9
dc.subjectCancer subtypes
dc.subjectGastric adenocarcinoma
dc.subjectGastric cancer
dc.subjectMolecular
dc.subjectPrognosis
dc.subjectSurvival
dc.subjectCancer subtypes
dc.subjectGastric adenocarcinoma
dc.subjectGastric cancer
dc.subjectMolecular
dc.subjectPrognosis
dc.subjectSurvival
dc.subjectSDG 3 - Good Health and Well-being
dc.titleHigh proportion of potential candidates for immunotherapy in a chilean cohort of gastric cancer patients: Results of the FORCE1 studyeng
dc.typeArticleeng
dc.typeArtículospa
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