Oncotarget

Research Papers:

Telomeric repeat-binding factor 2: a marker for survival and anti-EGFR efficacy in oral carcinoma

Yordan Benhamou, Vincent Picco, Hélène Raybaud, Anne Sudaka, Emmanuel Chamorey, Sanja Brolih, Martino Monteverde, Marco Merlano, Cristiana Lo Nigro, Damien Ambrosetti and Gilles Pagès _

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Oncotarget. 2016; 7:44236-44251. https://doi.org/10.18632/oncotarget.10005

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Abstract

Yordan Benhamou1,3,*, Vincent Picco2,*, Hélène Raybaud4, Anne Sudaka5, Emmanuel Chamorey5, Sanja Brolih2, Martino Monteverde6, Marco Merlano7, Cristiana Lo Nigro6, Damien Ambrosetti4, Gilles Pagès1

1CNRS UMR 7284/INSERM U1081, Institute for Research on Cancer and Aging of Nice, University of Nice Sophia Antipolis, Nice, France

2Biomedical Department, Centre Scientifique de Monaco, Principality of Monaco

3Odontology Department, Nice University Hospital, University of Nice Sophia Antipolis, Nice, France

4Central Laboratory of Pathology, University of Nice Sophia Antipolis, Nice, France

5Department of Pathology, Research and Statistics, Centre Antoine Lacassagne, Nice, France

6Cancer Genetics and Translational Oncology Laboratory, S. Croce & Carle Teaching Hospital, Cuneo, Italy

7Medical Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy

*These authors have contributed equally to this work

Correspondence to:

Gilles Pagès, email: gpages@unice.fr

Keywords: prognostic factor, predictive factor, oral cancer, tumor microenvironment, targeted therapies

Received: January 21, 2016    Accepted: May 04, 2016    Published: June 14, 2016

ABSTRACT

Oral Squamous Cell Carcinoma (OSCC) is the most common oral cancer worldwide. Treatments including surgery, radio- and chemo-therapies mostly result in debilitating side effects. Thus, a more accurate evaluation of patients at risk of recurrence after radio/chemo treatment is important for preserving their quality of life. We assessed whether the Telomeric Repeat-binding Factor 2 (TERF2) influences tumor aggressiveness and treatment response. TERF2 is over-expressed in many cancers but its correlation to patient outcome remains controversial in OSCC. Our retrospective study on sixty-two patients showed that TERF2 overexpression has a negative impact on survival time. TERF2-dependent survival time was independent of tumor size in a multivariate analysis. In vitro, TERF2 knockdown by RNA interference had no effect on cell proliferation, migration, senescence and apoptosis. Instead, TERF2 knockdown increased the expression of cytokines implicated in inflammation and angiogenesis, except for vascular endothelial growth factor. TERF2 knockdown resulted in a decrease vascularization and growth of xenograft tumors. Finally, response to erlotinib/Tarceva and cetuximab/Erbitux treatment was increased in TRF2 knocked-down cells. Hence, TERF2 may represent an independent marker of survival for OSCC and a predictive marker for cetuximab/Erbitux and erlotinib/Tarceva efficacy.


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