Miguel Angel Pavón1,2, Irene Arroyo-Solera3,4, Xavier León4,5, Marta Téllez-Gabriel6, David Virós7, Alberto Gallardo8, Maria Virtudes Céspedes3,4, Isolda Casanova3,4, Antonio Lopez-Pousa4,9, Agustí Barnadas9, Miquel Quer5, Ramón Mangues3,4. 1. Infections and Cancer Laboratory/Cancer Epidemiology Research Program. Catalan Institute of Oncology (ICO) and Bellvitge Institute of Biomedical Research (IDIBELL), Barcelona, Spain. 2. Centro de Investigación Biomédica en Red en Cáncer (CIBER-ONC), Madrid, Spain. 3. Oncogenesis and Antitumor Drug Group, lnstitut d'Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Barcelona, Spain. 4. Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomecidicina (CIBER-BBN), Madrid, Spain. 5. Department of Otorrinolaryngology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 6. Laboratorio Hematología Oncológica y de Transplantes, Institut Investigacions Biomèdiques (IBB) Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 7. Department of Otorrinolaryngology, Hospital Germans Tries y Pujol (Can Ruti), Barcelona, Spain. 8. Department of Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 9. Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Abstract
BACKGROUND: We aimed at identifying molecular markers predictive of clinical outcome in patients with head and neck cancer based on the expression profile of cells showing epithelial-like (EL) or mesenchymal-like (ML) phenotypes. MATERIALS AND METHODS: We analyzed the association between EL and ML cells and migration, drug resistance, or tumor growth. The differential gene expression profile between cell types was used to build a model to stratify patients according to survival. RESULTS: EL cells were sensitive to cisplatin and cetuximab, showed low migration, and generated squamous differentiated tumors in mouse. A differential 93-gene expression signature between ML and EL cells was used to build a three-gene (EFS, GPX2, and SPRR1A) survival model by analyzing the RNA-seq data of the TCGA-HNSC project. Its prognostic value was confirmed in two independent cohorts. CONCLUSION: EFS, GPX2, and SPRR1A are prognostic markers able to distinguish clinical outcome among subtypes sharing an EL phenotype.
BACKGROUND: We aimed at identifying molecular markers predictive of clinical outcome in patients with head and neck cancer based on the expression profile of cells showing epithelial-like (EL) or mesenchymal-like (ML) phenotypes. MATERIALS AND METHODS: We analyzed the association between EL and ML cells and migration, drug resistance, or tumor growth. The differential gene expression profile between cell types was used to build a model to stratify patients according to survival. RESULTS: EL cells were sensitive to cisplatin and cetuximab, showed low migration, and generated squamous differentiated tumors in mouse. A differential 93-gene expression signature between ML and EL cells was used to build a three-gene (EFS, GPX2, and SPRR1A) survival model by analyzing the RNA-seq data of the TCGA-HNSC project. Its prognostic value was confirmed in two independent cohorts. CONCLUSION:EFS, GPX2, and SPRR1A are prognostic markers able to distinguish clinical outcome among subtypes sharing an EL phenotype.