title: Enhanced cell migration and apoptosis resistance may underlie the association between high SERPINE1 expression and poor outcome in head and neck carcinoma patients.
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.
authors.affiliation: Grup d'Oncogènesi i Antitumorals, lnstitut 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.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Pavón
authors.affiliation: Grup d'Oncogènesi i Antitumorals, lnstitut 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.
authors.forename: Irene
authors.initials: I
authors.lastname: Arroyo-Solera
authors.affiliation: Grup d'Oncogènesi i Antitumorals, lnstitut 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.
authors.forename: Marta
authors.initials: M
authors.lastname: Téllez-Gabriel
authors.affiliation: 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.
authors.forename: Xavier
authors.initials: X
authors.lastname: León
authors.affiliation: Department of Otorrinolaryngology, Hospital Moises Broggi, Sant Joan Despí, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Virós
authors.affiliation: Department of Otorrinolaryngology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: López
authors.affiliation: Department of Pathology, Clínica Girona, Girona, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Gallardo
authors.affiliation: Grup d'Oncogènesi i Antitumorals, lnstitut 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.
authors.forename: Maria Virtudes
authors.initials: MV
authors.lastname: Céspedes
authors.affiliation: Grup d'Oncogènesi i Antitumorals, lnstitut 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.
authors.forename: Isolda
authors.initials: I
authors.lastname: Casanova
authors.affiliation: 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.
authors.forename: Antonio
authors.initials: A
authors.lastname: López-Pousa
authors.affiliation: Department of Pharmacy, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Maria Antonia
authors.initials: MA
authors.lastname: Mangues
authors.affiliation: Department of Otorrinolaryngology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Quer
authors.affiliation: Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Agustí
authors.initials: A
authors.lastname: Barnadas
authors.affiliation: Grup d'Oncogènesi i Antitumorals, lnstitut 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.
authors.forename: Ramón
authors.initials: R
authors.lastname: Mangues
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000494:pharmacology; D030541:Databases, Genetic; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D012189:Retrospective Studies; D012307:Risk Factors; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D013997:Time Factors; D014162:Transfection; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin
keywords: AKT; HNSCC; SERPINE1; biomarker; prognosis