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

2016; Impact Journals LLC; Volume: 7; Issue: 30 Linguagem: Inglês

10.18632/oncotarget.10163

1949-2553

Marie-Paule Sablin, Coraline Dubot, Jerzy Klijanienko, Sophie Vacher, Lamia Ouafi, Walid Chemlali, Martial Caly, Xavier Sastre‐Garau, Emmanuelle Lappartient, Odette Mariani, José Rodriguez, Thomas Jouffroy, Angélique Girod, Valentin Calugaru, Caroline Hoffmann, Rosette Lidereau, Frédérique Berger, Maud Kamal, Ivan Bièche, Christophe Le Tourneau,

Head and Neck Cancer Studies

// 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.