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Prognostic significance of NDRG1 expression in oral and oropharyngeal squamous cell carcinoma

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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.

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Acknowledgments

The GENCAPO group acknowledges the financial support from Fundação de Amparo à Pesquisa do Estado de São Paulo/FAPESP (Grants 04/12054-9), and Associação Beneficente Alzira Denise Hertzog Silva/ABADHS, and the researcher fellowships from Conselho Nacional de Pesquisas (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Instituto Israelita de Ensino e Pesquisa Albert Einstein, and The Ludwig Institute for Cancer Research. Fundação de Amparo à Pesquisa do Estado de São Paulo/FAPESP (Grant 04/12054-9).

Conflicts of interest

Authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Universidade Federal do Espírito Santo, Avenida Marechal Campos, 1468, Maruípe, Vitória, ES, CEP 29043-900, Brazil

    Marcelo dos Santos

  2. Laboratório de Biologia Molecular do Hospital Heliópolis, Rua Cônego Xavier, 276, Sacomã, São Paulo, SP, CEP 04231-030, Brazil

    Marcelo dos Santos, Marcos Brasilino de Carvalho, Diana Gazito, Paulo Bentes de Carvalho Neto & Adriana Madeira Álvares da Silva

  3. Anatomia Patológica do Hospital Heliópolis, Rua Cônego Xavier, 276, Sacomã, São Paulo, SP, CEP 04231-030, Brazil

    Ana Maria da Cunha Mercante & Paula Blandina Olga Chiappini

  4. Departamento de Estomatologia, Faculdade de Odontologia da Universidade de São Paulo, Avenida Prof. Lineu Prestes, 2227, Cidade Universitária, São Paulo, SP, CEP 05508-000, Brazil

    Fábio Daumas Nunes

  5. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas da Universidade de São Paulo, Avenida do Café, s/n, Campus Universitário, Ribeirão Preto, SP, CEP 14040-903, Brazil

    Andréia Machado Leopoldino

  6. Departamento de Ciências Biológicas, Núcleo de Genética Humana e Molecular, Universidade Federal do Espírito Santo, Avenida Marechal Campos, 1468, Maruípe, Vitória, ES, CEP 29043-900, Brazil

    Iúri Drumond Louro

  7. Departamento de Epidemiologia, Faculdade de Saúde Pública da Universidade de São Paulo, Avenida Doutor Arnaldo, 715, São Paulo, SP, CEP 01255-000, Brazil

    Rossana Verónica Mendoza López

  8. Instituto do Câncer Arnaldo Vieira de Carvalho, Rua Doutor Cesário Motta Júnior, 112, Vila Buarque, São Paulo, SP, CEP 01221-020, Brazil

    Erica Erina Fukuyama

  9. Departamento de Biologia Molecular, Faculdade de Medicina, Avenida Brigadeiro Faria Lima, 5416, Vila São Pedro, São José do Rio Preto, SP, CEP 15090-000, Brazil

    Eloiza Helena Tajara

  10. Departamento de Genética e Biologia Evolutiva, Instituto de Biociências da Universidade de São Paulo, Rua do Matão, 321, Cidade Universitária, São Paulo, SP, CEP 05508-090, Brazil

    Eloiza Helena Tajara

  11. Departamento de Produção Vegetal/Biologia, Universidade Federal do Espírito Santo-DPV/Biologia, Alto Universitário s/n, Alto Universitário, Caixa Postal 16, Alegre, ES, CEP 29500-000, Brazil

    Adriana Madeira Álvares da Silva

Authors
  1. Marcelo dos Santos
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  2. Ana Maria da Cunha Mercante
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  3. Fábio Daumas Nunes
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  4. Andréia Machado Leopoldino
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  5. Marcos Brasilino de Carvalho
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  6. Diana Gazito
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  7. Rossana Verónica Mendoza López
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  8. Paula Blandina Olga Chiappini
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  9. Paulo Bentes de Carvalho Neto
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  10. Erica Erina Fukuyama
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  11. Eloiza Helena Tajara
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  12. Iúri Drumond Louro
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  13. Adriana Madeira Álvares da Silva
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Head Neck Genome Project/GENCAPO

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Correspondence to Adriana Madeira Álvares da Silva.

Appendix

Appendix

The GENCAPO (Head and Neck Genome) Project authors are the following: Cury PM7, de Carvalho MB8, Dias-Neto E3, Figueiredo DLA9, Fukuyama EE5, Góis-Filho JF5, Leopoldino AM15, Mamede RCM9, Michaluart-Junior P6, Moreira-Filho CA17, Moyses RA6, Nóbrega FG4, Nóbrega MP4, Nunes FD13, Ojopi EPB3, Okamoto OK14, Serafini LN10, Severino P1, Silva AMA8,18, Silva Jr WA11, Silveira NJF16, Souza SCOM13, Tajara EH2, Wünsch-Filho V12, Amar A8, Arap SS6, Araújo NSS6, Araújo-Filho V6, Barbieri RB8, Bastos AU8, Brandão LG6, Brandão RM11, Canto AL4, Carmona-Raphe J2, Carvalho Neto PB8, Casemiro AF8, Cerione M5, Cernea CR6, Cicco R5, Chedid H8, Chiappini PBO8, Correia LA8, Costa A12, Costa ACW8, Cunha BR2, Curioni OA8, Dias THG3, Durazzo M6, Ferraz AR6, Figueiredo RO12, Fortes CS12, Franzi SA8, Frizzera APZ7, Gallo J6, Gazito D8, Guimarães PEM6, Gutierres AP8, Henrique T2, Inamine R12, Kaneto CM11, Lehn CN8, López RVM12, Macarenco R4, Magalhães RP6, Magalhães MR8, Martins AE8, Meneses C4, Mercante AMC8, Montenegro FLM6, Pinheiro DG11, Polachini GM2, Porsani AF8, Rapoport A8, Rodini CO13, Rodrigues AN12, Rodrigues-Lisoni FC2, Rodrigues RV2, Rossi L8, Santos ARD11, Santos M8, Settani F5, Silva FAM15, Silva IT11, Silva-Filho GB6, Smith RB6, Souza TB8, Stabenow E6, Takamori JT8, Tavares MR6, Turcano R6, Valentim PJ5, Vidotto A2, Volpi EM6, Xavier FCA13, Yamagushi F5, Bogossian AP4, Cominato ML5, Correa PMS4, Mendes GS5, Paiva R5, Ramos O6, Silva C6, Silva MJ5, Tarlá MVC11, Santos VPP8, Dutra RL8, Alves JL8, Campos JC8, Runga DS8. Affiliations 1Instituto de Ensino e Pesquisa Albert Einstein, São Paulo; 2Departamento de Biologia Molecular, Faculdade de Medicina de São José do Rio Preto; 3Departamento e Instituto de Psiquiatria, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo; 4Departamento de Biociências e Diagnóstico Bucal, Faculdade de Odontologia, Universidade Estadual Paulista, São José dos Campos, São Paulo, 5Serviço de Cirurgia de Cabeça e Pescoço, Instituto do Câncer Arnaldo Vieira de Carvalho, São Paulo; 6Departamento de Cirurgia de Cabeça e Pescoço, Faculdade de Medicina, USP, São Paulo; 7Departamento de Patologia, Faculdade de Medicina de São José do Rio Preto; 8Hospital Heliópolis, São Paulo; 9Serviço de Cirurgia de Cabeça e Pescoço, Faculdade de Medicina de Ribeirão Preto, USP; 10Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, USP; 11Departamento de Genética, Faculdade de Medicina de Ribeirão Preto, USP; 12Departamento de Epidemiologia, Faculdade de Saúde Pública, USP, São Paulo; 13Departamento de Estomatologia, Faculdade de Odontologia da USP, São Paulo; 14Departamento de Neurologia/Neurocirurgia, UNIFESP, São Paulo; 15Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP; 16Instituto de Pesquisa e Desenvolvimento, UNIVAP, São José dos Campos; 17Departamento de Pediatria, Faculdade de Medicina, USP, São Paulo, SP, Brazil, 18Universidade Federal do Espírito Santo.

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dos Santos, M., da Cunha Mercante, A.M., Nunes, F.D. et al. Prognostic significance of NDRG1 expression in oral and oropharyngeal squamous cell carcinoma. Mol Biol Rep 39, 10157–10165 (2012). https://doi.org/10.1007/s11033-012-1889-0

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