Enhanced cell migration and apoptosis resistance may underlie the association between high SERPINE1 expression and poor outcome in head and neck carcinoma patients
Pavón, Miguel Ángel (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Arroyo Solera, Irene (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Téllez Gabriel, Marta (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
León i Vintró, Xavier (Institut d'Investigació Biomèdica Sant Pau)
Virós, David (Hospital de Sant Joan Despí Moisès Broggi)
López, Montserrat (Institut d'Investigació Biomèdica Sant Pau)
Gallardo, Alberto (Clínica Girona)
Céspedes, María Virtudes (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Casanova Rigat, Isolda (Institut d'Investigació Biomèdica Sant Pau)
López Pousa, Antonio (Institut d'Investigació Biomèdica Sant Pau)
Mangues, Ma Antonia (Institut d'Investigació Biomèdica Sant Pau)
Quer, Miquel (Institut d'Investigació Biomèdica Sant Pau)
Barnadas i Molins, Agustí (Institut d'Investigació Biomèdica Sant Pau)
Mangues, Ramon 1957- (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona. Departament de Medicina

Date:	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.
Grants:	Ministerio de Ciencia e Innovación PI11/00525 Ministerio de Economía y Competitividad PI12/01861 Ministerio de Economía y Competitividad PI14/01918
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	AKT ; Biomarker ; HNSCC ; Prognosis ; SERPINE1
Published in:	Oncotarget, Vol. 6 Núm. 30 (2015) , p. 29016-29033, ISSN 1949-2553

DOI: 10.18632/oncotarget.5032
PMID: 26359694

18 p, 8.2 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles