Identification of new candidate therapeutic target genes in head and neck squamous cell carcinomas
Metrics: PDF 1439 views | HTML 1794 views | ?
Marie-Paule Sablin1,*, Coraline Dubot1,2,*, Jerzy Klijanienko3, Sophie Vacher2, Lamia Ouafi3, Walid Chemlali2, Martial Caly3, Xavier Sastre-Garau3, Emmanuelle Lappartient3, Odette Mariani3, José Rodriguez4, Thomas Jouffroy4, Angélique Girod4, Valentin Calugaru5, Caroline Hoffmann4, Rosette Lidereau2, Frédérique Berger4,6, Maud Kamal1, Ivan Bieche2,7, Christophe Le Tourneau1,8
1Department of Medical Oncology, Institut Curie, Paris and Saint-Cloud, France
2Unit of Pharmacogenomics, Department of Genetics, Institut Curie, Paris, France
3Department of Biopathology, Institut Curie, Paris, France
4Department of Surgery, Institut Curie, Paris, France
5Department of Radiotherapy, Institut Curie, Paris, France
6Department of Biostatistics, Institut Curie, Paris, France
7EA7331, Paris Descartes University, Sorbonne Paris Cité, Faculty of Pharmaceutical and Biological Sciences, Paris, France
8EA7285, Versailles-Saint-Quentin-en-Yvelines University, Versailles, France
*These authors equally contributed to this work
Coraline Dubot, email: [email protected]
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
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.