Enhanced cell migration and apoptosis resistance may underlie the association between high SERPINE1 expression and poor outcome in head and neck carcinoma patients
Por:
Pavón M.A., Arroyo-Solera I., Téllez-Gabriel M., León X., Virós D., López M., Gallardo A., Céspedes M.V., Casanova I., López-Pousa A., Mangues M.A., Quer M., Barnadas A., Mangues R.
Publicada:
1 ene 2015
Resumen:
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.
Filiaciones:
Pavón M.A.:
Grup d'Oncogènesi i Antitumorals, Institut d'Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Barcelona, Spain
Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomecidicina (CIBER-BBN), Barcelona, Spain
Arroyo-Solera I.:
Grup d'Oncogènesi i Antitumorals, Institut d'Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Barcelona, Spain
Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomecidicina (CIBER-BBN), Barcelona, Spain
Téllez-Gabriel M.:
Grup d'Oncogènesi i Antitumorals, Institut d'Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Barcelona, Spain
Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomecidicina (CIBER-BBN), Barcelona, Spain
León X.:
Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomecidicina (CIBER-BBN), Barcelona, Spain
Department of Otorrinolaryngology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Virós D.:
Department of Otorrinolaryngology, Hospital Moises Broggi, Sant Joan Despí, Spain
López M.:
Department of Otorrinolaryngology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Gallardo A.:
Department of Pathology, Clínica Girona, Girona, Spain
Céspedes M.V.:
Grup d'Oncogènesi i Antitumorals, Institut d'Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Barcelona, Spain
Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomecidicina (CIBER-BBN), Barcelona, Spain
Casanova I.:
Grup d'Oncogènesi i Antitumorals, Institut d'Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Barcelona, Spain
Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomecidicina (CIBER-BBN), Barcelona, Spain
López-Pousa A.:
Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomecidicina (CIBER-BBN), Barcelona, Spain
Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Mangues M.A.:
Department of Pharmacy, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Quer M.:
Department of Otorrinolaryngology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Barnadas A.:
Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Mangues R.:
Grup d'Oncogènesi i Antitumorals, Institut d'Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Barcelona, Spain
Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomecidicina (CIBER-BBN), Barcelona, Spain
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