Identification of Thrombosis-Related Genes in Patients with Advanced Gastric Cancer: Data from AGAMENON-SEOM Registry
David Zaragoza-Huesca,
Pedro Garrido-Rodríguez,
Paula Jiménez-Fonseca,
Eva Martínez de Castro,
Manuel Sánchez-Cánovas,
Laura Visa,
Ana Custodio,
Ana Fernández-Montes,
Julia Peñas-Martínez,
Patricia Morales del Burgo,
Javier Gallego,
Ginés Luengo-Gil,
Vicente Vicente,
Irene Martínez-Martínez,
Alberto Carmona-Bayonas
Affiliations
David Zaragoza-Huesca
Centro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30003 Murcia, Spain
Pedro Garrido-Rodríguez
Centro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30003 Murcia, Spain
Paula Jiménez-Fonseca
Department of Medical Oncology, Instituto de Investigación Sanitaria del Principado de Asturias—ISPA, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain
Eva Martínez de Castro
Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla, 39008 Santander, Spain
Manuel Sánchez-Cánovas
Centro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30003 Murcia, Spain
Laura Visa
Department of Medical Oncology, Hospital del Mar, 08003 Barcelona, Spain
Ana Custodio
Department of Medical Oncology, Hospital Universitario La Paz, CIBERONC CB16/12/00398, 28046 Madrid, Spain
Ana Fernández-Montes
Department of Medical Oncology, Complejo Hospitalario Universitario de Ourense, 32005 Ourense, Spain
Julia Peñas-Martínez
Centro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30003 Murcia, Spain
Patricia Morales del Burgo
Department of Pathology, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain
Javier Gallego
Department of Medical Oncology, Hospital General Universitario de Elche, 03203 Elche, Spain
Ginés Luengo-Gil
Centro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30003 Murcia, Spain
Vicente Vicente
Centro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30003 Murcia, Spain
Irene Martínez-Martínez
Centro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30003 Murcia, Spain
Alberto Carmona-Bayonas
Centro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30003 Murcia, Spain
Advanced gastric cancer is one of the most thrombogenic neoplasms. However, genetic mechanisms underlying this complication remain obscure, and the molecular and histological heterogeneity of this neoplasm hinder the identification of thrombotic biomarkers. Therefore, our main objective was to identify genes related to thrombosis regardless of Lauren subtypes. Furthermore, in a secondary exploratory study, we seek to discover thrombosis-associated genes that were specific to each TCGA molecular subtype. We designed a nested case-control study using the cohort of the AGAMENON national advanced gastric cancer registry. Ninety-seven patients were selected—48 with and 49 without venous thromboembolism (using propensity score matching to adjust for confounding factors)—and a differential gene expression array stratified by Lauren histopathological subtypes was carried out in primary tumor samples. For the secondary objective, the aforementioned differential expression analysis was conducted for each TCGA group. Fifteen genes were determined to be associated with thrombosis with the same expression trend in both the intestinal and diffuse subtypes. In thrombotic subjects, CRELD1, KCNH8, CRYGN, MAGEB16, SAA1, ARL11, CCDC169, TRMT61A, RIPPLY3 and PLA2G6 were underexpressed (adjusted-p PRKD3, MIR5683, SDCBP, EPS8 and CDC45 were overexpressed (adjusted-p < 0.05), and correlated, by logistic regression, with lower or higher thrombotic risk, respectively, in the overall cohort. In each TCGA molecular subtype, we identified a series of genes differentially expressed in thrombosis that appear to be subtype-specific. We have identified several genes associated with venous thromboembolism in advanced gastric cancer that are common to Lauren intestinal and diffuse subtypes. Should these genetic factors be validated in the future, they could be complemented with existing clinical models to bolster the ability to predict thrombotic risk in individuals with advanced gastric adenocarcinoma.
