Oncotarget

Research Papers:

Enhanced cell migration and apoptosis resistance may underlie the association between high SERPINE1 expression and poor outcome in head and neck carcinoma patients

Miguel Angel Pavón _, Irene Arroyo-Solera, Marta Téllez-Gabriel, Xavier León, David Virós, Montserrat López, Alberto Gallardo, Maria Virtudes Céspedes, Isolda Casanova, Antonio López-Pousa, Maria Antonia Mangues, Miquel Quer, Agustí Barnadas and Ramón Mangues

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Oncotarget. 2015; 6:29016-29033. https://doi.org/10.18632/oncotarget.5032

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Abstract

Miguel Angel Pavón1,2,#, Irene Arroyo-Solera1,2,#, Marta Téllez-Gabriel1,2, Xavier León2,3, David Virós4, Montserrat López3, Alberto Gallardo5, Maria Virtudes Céspedes1,2, Isolda Casanova1,2, Antonio López-Pousa2,6, Maria Antonia Mangues7, Miquel Quer3, Agustí Barnadas6, Ramón Mangues1,2

1Grup d’Oncogènesi i Antitumorals, lnstitut d’Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Barcelona, Spain

2Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomecidicina (CIBER-BBN), Barcelona, Spain

3Department of Otorrinolaryngology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

4Department of Otorrinolaryngology, Hospital Moises Broggi, Sant Joan Despí, Spain

5Department of Pathology, Clínica Girona, Girona, Spain

6Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

7Department of Pharmacy, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

#These authors contributed equally to this study

Correspondence to:

Ramón Mangues, e-mail: rmangues@santpau.cat

Keywords: HNSCC, SERPINE1, prognosis, biomarker, AKT

Received: April 14, 2015     Accepted: August 14, 2015     Published: August 24, 2015

ABSTRACT

High SERPINE1 expression is a common event in head and neck squamous cell carcinoma (HNSCC); however, whether it plays a role in determining clinical outcome remains still unknown. We studied SERPINE1 as a prognostic marker in two HNSCC patient cohorts. In a retrospective study (n = 80), high expression of SERPINE1 was associated with poor progression-free (p = 0.022) and cancer-specific (p = 0.040) survival. In a prospective study (n = 190), high SERPINE1 expression was associated with poor local recurrence-free (p = 0.022), progression-free (p = 0.002) and cancer-specific (p = 0.006) survival. SERPINE1 expression was identified as an independent risk factor for progression-free survival in patients treated with chemo-radiotherapy or radiotherapy (p = 0.043). In both patient cohorts, high SERPINE1 expression increased the risk of metastasis spread (p = 0.045; p = 0.029). The association between SERPINE1 expression and survival was confirmed using the HNSCC cohort included in The Cancer Genome Atlas project (n = 507). Once again, patients showing high expression had a poorer survival (p < 0.001). SERPINE1 over-expression in HNSCC cells reduced cell proliferation and enhanced migration. It also protected cells from cisplatin-induced apoptosis, which was accompanied by PI3K/AKT pathway activation. Downregulation of SERPINE1 expression had the opposite effect.

We propose SERPINE1 expression as a prognostic marker that could be used to stratify HNSCC patients according to their risk of recurrence.


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