Enhanced cell migration and apoptosis resistance may underlie the association between high SERPINE1 expression and poor outcome in head and neck carcinoma patients
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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
Ramón Mangues, e-mail: firstname.lastname@example.org
Keywords: HNSCC, SERPINE1, prognosis, biomarker, AKT
Received: April 14, 2015 Accepted: August 14, 2015 Published: August 24, 2015
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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