Oncotarget

Research Papers:

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

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 Bieche and Christophe Le Tourneau

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Oncotarget. 2016; 7:47418-47430. https://doi.org/10.18632/oncotarget.10163

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Abstract

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

Correspondence to:

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

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.


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