Identification of new candidate therapeutic target genes in head and neck squamous cell carcinomas

Abstract

// Marie-Paule Sablin 1, * , Coraline Dubot 1, 2, * , Jerzy Klijanienko 3 , Sophie Vacher 2 , Lamia Ouafi 3 , Walid Chemlali 2 , Martial Caly 3 , Xavier Sastre-Garau 3 , Emmanuelle Lappartient 3 , Odette Mariani 3 , José Rodriguez 4 , Thomas Jouffroy 4 , Angélique Girod 4 , Valentin Calugaru 5 , Caroline Hoffmann 4 , Rosette Lidereau 2 , Frédérique Berger 4, 6 , Maud Kamal 1 , Ivan Bieche 2, 7 , Christophe Le Tourneau 1, 8 1 Department of Medical Oncology, Institut Curie, Paris and Saint-Cloud, France 2 Unit of Pharmacogenomics, Department of Genetics, Institut Curie, Paris, France 3 Department of Biopathology, Institut Curie, Paris, France 4 Department of Surgery, Institut Curie, Paris, France 5 Department of Radiotherapy, Institut Curie, Paris, France 6 Department of Biostatistics, Institut Curie, Paris, France 7 EA7331, Paris Descartes University, Sorbonne Paris Cité, Faculty of Pharmaceutical and Biological Sciences, Paris, France 8 EA7285, Versailles-Saint-Quentin-en-Yvelines University, Versailles, France * These authors equally contributed to this work Correspondence to: Coraline Dubot, email: coraline.dubot@curie.fr Keywords: head and neck squamous cell carcinoma, gene expression, clinical prognostic and theranognostic biomarkers Received: January 21, 2016      Accepted: June 01, 2016      Published: June 18, 2016 ABSTRACT Background: We aimed at identifying druggable molecular alterations at the RNA level from untreated HNSCC patients, and assessing their prognostic significance. Methods: We retrieved 96 HNSCC patients who underwent primary surgery. Real-time quantitative RT-PCR was used to analyze a panel of 42 genes coding for major druggable proteins. Univariate and multivariate analyses were performed to assess the prognostic significance of overexpressed genes. Results: Median age was 56 years [35–78]. Most of patients were men (80%) with a history of alcohol (70.4%) and/or tobacco consumption (72.5%). Twelve patients (12%) were HPV-positive. Most significantly overexpressed genes involved cell cycle regulation (CCND1 [27%], CDK6 [21%]), tyrosine kinase receptors ( MET [18%], EGFR [14%]), angiogenesis ( PGF [301%], VEGFA [14%]), and immune system ( PDL1/CD274 [28%]). PIK3CA expression was an independent prognostic marker, associated with shorter disease-free survival. Conclusions: We identified druggable overexpressed genes associated with a poor outcome that might be of interest for personalizing treatment of HNSCC patients.