title: Telomeric repeat-binding factor 2: a marker for survival and anti-EGFR efficacy in oral carcinoma.
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.
authors.affiliation: CNRS UMR 7284/INSERM U1081, Institute for Research on Cancer and Aging of Nice, University of Nice Sophia Antipolis, Nice, France.|Odontology Department, Nice University Hospital, University of Nice Sophia Antipolis, Nice, France.
authors.forename: Yordan
authors.initials: Y
authors.lastname: Benhamou
authors.affiliation: Biomedical Department, Centre Scientifique de Monaco, Principality of Monaco.
authors.forename: Vincent
authors.initials: V
authors.lastname: Picco
authors.affiliation: Central Laboratory of Pathology, University of Nice Sophia Antipolis, Nice, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Raybaud
authors.affiliation: Department of Pathology, Research and Statistics, Centre Antoine Lacassagne,  Nice, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Sudaka
authors.affiliation: Department of Pathology, Research and Statistics, Centre Antoine Lacassagne,  Nice, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Chamorey
authors.affiliation: Biomedical Department, Centre Scientifique de Monaco, Principality of Monaco.
authors.forename: Sanja
authors.initials: S
authors.lastname: Brolih
authors.affiliation: Cancer Genetics and Translational Oncology Laboratory, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Martino
authors.initials: M
authors.lastname: Monteverde
authors.affiliation: Medical Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Merlano
authors.affiliation: Cancer Genetics and Translational Oncology Laboratory, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Lo Nigro
authors.affiliation: Central Laboratory of Pathology, University of Nice Sophia Antipolis, Nice, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Ambrosetti
authors.affiliation: CNRS UMR 7284/INSERM U1081, Institute for Research on Cancer and Aging of Nice, University of Nice Sophia Antipolis, Nice, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Pagès
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D000068818:Cetuximab / Q000008:administration & dosage; D015536:Down-Regulation; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage; D005260:Female; D055785:Gene Knockdown Techniques; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck; D035341:Telomeric Repeat Binding Protein 2 / Q000096:biosynthesis* / Q000235:genetics; D059016:Tumor Microenvironment; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; C504753:TERF2 protein, human; D035341:Telomeric Repeat Binding Protein 2; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab
keywords: oral cancer; predictive factor; prognostic factor; targeted therapies; tumor microenvironment