title: Prognostic significance of NDRG1 expression in oral and oropharyngeal squamous cell carcinoma.
abstract: Human N-myc downstream-regulated gene 1 (NDRG1) is a metastasis suppressor gene with several potential functions, including cell differentiation, cell cycle regulation and response to hormones, nickel and stress. The purpose of this study was to investigate the immunoexpression of NDRG1 in oral and oropharyngeal squamous cell carcinomas searching for its role in the clinical course of these tumors. We investigated immunohistochemical expression of NDRG1 protein in 412 tissue microarray cores of tumor samples from 103 patients with oral and oropharyngeal squamous cell carcinomas and in 110 paraffin-embedded surgical margin sections. The results showed NDRG1 up-regulation in 101/103 (98.1 %) tumor samples, but no expression in any normal tissue sample. Western blot assays confirmed the immunohistochemical findings, suggesting that lower levels of NDRG1 are associated with a high mortality rate. NDRG1 overexpression was related to long-term specific survival (HR = 0.38; p = 0.009), whereas the presence of lymph-node metastasis showed the opposite association with survival (HR = 2.45; p = 0.013). Our findings reinforce the idea that NDRG1 plays a metastasis suppressor role in oral and oropharyngeal squamous cell carcinomas and may be a useful marker for these tumors.
authors.affiliation: Universidade Federal do Espírito Santo, Avenida Marechal Campos, 1468, Maruípe, Vitória, ES, CEP 29043-900, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Dos Santos
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: da Cunha Mercante
authors.forename: Fábio Daumas
authors.initials: FD
authors.lastname: Nunes
authors.forename: Andréia Machado
authors.initials: AM
authors.lastname: Leopoldino
authors.forename: Marcos Brasilino
authors.initials: MB
authors.lastname: de Carvalho
authors.forename: Diana
authors.initials: D
authors.lastname: Gazito
authors.forename: Rossana Verónica Mendoza
authors.initials: RV
authors.lastname: López
authors.forename: Paula Blandina Olga
authors.initials: PB
authors.lastname: Chiappini
authors.forename: Paulo Bentes
authors.initials: PB
authors.lastname: de Carvalho Neto
authors.forename: Erica Erina
authors.initials: EE
authors.lastname: Fukuyama
authors.forename: Eloiza Helena
authors.initials: EH
authors.lastname: Tajara
authors.forename: Iúri Drumond
authors.initials: ID
authors.lastname: Louro
authors.forename: Adriana Madeira Álvares
authors.initials: AM
authors.lastname: da Silva
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009959:Oropharyngeal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D046888:Tissue Array Analysis; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein