title: High RAB25 expression is associated with good clinical outcome in patients with locally advanced head and neck squamous cell carcinoma.
abstract: Currently there are no molecular markers able to predict clinical outcome in locally advanced head and neck squamous cell carcinoma (HNSCC). In a previous microarray study, RAB25 was identified as a potential prognostic marker. The aim of this study was to analyze the association between RAB25 expression and clinical outcome in patients with locally advanced HNSCC treated with standard therapy. In a retrospective immunohistochemical study (n = 97), we observed that RAB25-negative tumors had lower survival (log-rank, P = 0.01) than patients bearing positive tumors. In an independent prospective mRNA study (n = 117), low RAB25 mRNA expression was associated with poor prognosis. Using classification and regression tree analysis (CART) we established two groups of patients according to their RAB25 mRNA level and their risk of death. Low mRNA level was associated with poor local recurrence-free (log-rank, P = 0.005), progression-free (log-rank, P = 0.002) and cancer-specific (log-rank, P < 0.001) survival. Multivariate Cox model analysis showed that low expression of RAB25 was an independent poor prognostic factor for survival (hazard ratio: 3.84, 95% confidence interval: 1.93-7.62, P < 0.001). Patients whose tumors showed high RAB25 expression had a low probability of death after treatment. We also found lower RAB25 expression in tumors than in normal tissue (Mann-Whitney U, P < 0.001). Moreover, overexpression of RAB25 in the UM-SCC-74B HNSCC cell line increased cisplatin sensitivity, and reduced cell migration and invasion. Our findings support a tumor suppressor role for RAB25 in HNSCC and its potential use to identify locally advanced patients with a high probability of survival after genotoxic treatment.
authors.affiliation: Grup d'Oncogènesi i Antitumorals (GOA), Institut d'Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Barcelona, Spain; Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Téllez-Gabriel
authors.forename: Irene
authors.initials: I
authors.lastname: Arroyo-Solera
authors.forename: Xavier
authors.initials: X
authors.lastname: León
authors.forename: Alberto
authors.initials: A
authors.lastname: Gallardo
authors.forename: Montserrat
authors.initials: M
authors.lastname: López
authors.forename: Maria V
authors.initials: MV
authors.lastname: Céspedes
authors.forename: Isolda
authors.initials: I
authors.lastname: Casanova
authors.forename: Antonio
authors.initials: A
authors.lastname: López-Pousa
authors.forename: Miquel
authors.initials: M
authors.lastname: Quer
authors.forename: Maria A
authors.initials: MA
authors.lastname: Mangues
authors.forename: Agustí
authors.initials: A
authors.lastname: Barnadas
authors.forename: Ramón
authors.initials: R
authors.lastname: Mangues
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Pavón
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D000077209:Decitabine; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome; D020691:rab GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D012333:RNA, Messenger; C509763:Rab25 protein, human; D000077209:Decitabine; D020691:rab GTP-Binding Proteins; D001374:Azacitidine; D002945:Cisplatin; D005472:Fluorouracil
keywords: HNSCC; RAB25; prognosis; tumor suppressor