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Homeobox gene expression profile indicates HOXA5 as a candidate prognostic marker in oral squamous cell carcinoma

Author(s): Rodini, Camila Oliveira ; Xavier, Flávia Caló Aquino ; Paiva, Katiúcia Batista Silva ; Destro, Maria Fernanda de Souza Setúbal ; Moyses, Raquel Ajub ; Michaluarte, Pedro ; Carvalho, Marcos Brasilino ; Fukuyama, Erica Erina ; Tajara, Eloiza Helena ; Okamoto, Oswaldo Keith ; Nunes, Fabio Daumas ; Cury, P. M. ; Carvalho, M. B. de ; Dias-Neto, E. ; Figueiredo, D. L. A. ; Góis-Filho, J. F. ; Leopoldino, A. M. ; Mamede, R. C. M. ; Michaluart, P. ; Moreira-Filho, C. A. ; Moyses, R. A. ; Nóbrega, F. G. [UNESP] ; Nóbrega, M. P. [UNESP] ; Nunes, F. D. ; Ojopi, E. P. B. ; Okamoto, O. K. ; Serafini, L. N. ; Severino, P. ; Silva, A. M. A. ; Silva, W. A. ; Silveira, N. J. F. ; Souza, S. C. O. M. ; Tajara, E. H. ; Wünsch-Filho, V. ; Zago, M. ; Amar, A. ; Arap, S. S. ; Araújo, N. S. S. ; Araújo-Filho, V. ; Barbieri, R. B. ; Bandeira, C. M. [UNESP] ; Bastos, A. U. ; Bogossian, A. P. [UNESP] ; Braconi, Ma [UNESP] ; Brandão, L. G. ; Brandão, R. M. ; Canto, A. L. [UNESP] ; Carvalho-Neto, P. B. ; Casemiro, A. F. ; Cerione, M. ; Cernea, C. R. ; Cicco, R. ; Chagas, M. J. [UNESP] ; Chedid, H. ; Chiappini, P. B. O. ; Correia, L. A. ; Costa, A. ; Costa, A. C. W. ; Cunha, B. R. ; Curioni, O. A. ; Dias, T. H. G. ; Durazzo, M. ; Ferraz, A. R. ; Figueiredo, R. O. ; Fortes, C. S. ; Franzi, S. A. ; Frizzera, A. P. Z. ; Gallo, J. ; Gazito, D. ; Guimarães, P. E. M. ; Gutierres, A. P. ; Inamine, R. ; Kaneto, C. M. ; Lehn, C. N. ; López, R. V. M. ; Macarenco, R. [UNESP] ; Magalhães, R. P. ; Martins, A. E. ; Meneses, C. [UNESP] ; Mercante, A. M. C. ; Montenegro, F. L. M. ; Pinheiro, D. G. ; Polachini, G. M. ; Porsani, A. F. ; Rapoport, A. ; Rodini, C. O. ; Rodrigues, A. N. ; Rodrigues-Lisoni, F. C. ; Rodrigues, R. V. ; Rossi, L. ; Santos, A. R. D. ; Santos, M. ; Settani, F. ; Silva, F. A. M. ; Silva, I. T. ; Silva-Filho, G. B. ; Smith, R. B. ; Souza, T. B. ; Stabenow, E. ; Takamori, J. T. ; Tavares, M. R. ; Turcano, R. ; Valentim, P. J. ; Volpi, E. M. ; Xavier, F. C. A. ; Yamagushi, F. ; Cominato, M. L. ; Correa, P. M. S. [UNESP] ; Mendes, G. S. ; Paiva, R. ; Ramos, O. ; Silva, C. ; Silva, M. J. ; Tarlá, M. V. C.

Date: 2014

Persistent ID: http://hdl.handle.net/11449/73253

Origin: Oasisbr

Subject(s): Homeobox genes; Hoxa5, prognosis; Oral cancer; homeodomain protein; Hox protein; messenger RNA; molecular marker; protein hoxa5; protein HOXD10; protein hoxd11; unclassified drug; adult; cancer cell culture; cancer survival; clinical article; controlled study; down regulation; gene expression profiling; genetic association; histopathology; human; human cell; human tissue; keratinocyte; microarray analysis; mouth carcinoma; oral squamous cell carcinoma; overall survival; pathogenesis; priority journal; prognosis; reverse transcription polymerase chain reaction; squamous cell carcinoma; upregulation; Adult; Aged; Carcinoma, Squamous Cell; Cell Line, Tumor; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Homeodomain Proteins; Humans; Middle Aged; Mouth Neoplasms; Prognosis; Survival Rate; Tumor Markers, Biological


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Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:26:26Z No. of bitstreams: 0

Made available in DSpace on 2014-05-27T11:26:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-04-01

The search for molecular markers to improve diagnosis, individualize treatment and predict behavior of tumors has been the focus of several studies. This study aimed to analyze homeobox gene expression profile in oral squamous cell carcinoma (OSCC) as well as to investigate whether some of these genes are relevant molecular markers of prognosis and/or tumor aggressiveness. Homeobox gene expression levels were assessed by microarrays and qRT-PCR in OSCC tissues and adjacent non-cancerous matched tissues (margin), as well as in OSCC cell lines. Analysis of microarray data revealed the expression of 147 homeobox genes, including one set of six at least 2-fold up-regulated, and another set of 34 at least 2-fold down-regulated homeobox genes in OSCC. After qRT-PCR assays, the three most up-regulated homeobox genes (HOXA5, HOXD10 and HOXD11) revealed higher and statistically significant expression levels in OSCC samples when compared to margins. Patients presenting lower expression of HOXA5 had poorer prognosis compared to those with higher expression (P=0.03). Additionally, the status of HOXA5, HOXD10 and HOXD11 expression levels in OSCC cell lines also showed a significant up-regulation when compared to normal oral keratinocytes. Results confirm the presence of three significantly upregulated (>4-fold) homeobox genes (HOXA5, HOXD10 and HOXD11) in OSCC that may play a significant role in the pathogenesis of these tumors. Moreover, since lower levels of HOXA5 predict poor prognosis, this gene may be a novel candidate for development of therapeutic strategies in OSCC.

Department of Oral Pathology School of Dentistry University of São Paulo, Av. Prof. Lineu Prestes 2227, Cidade Universitária, 05508-000 São Paulo

Department of Head and Neck Surgery School of Medicine University of São Paulo, Av. Dr. Arnaldo 455, Cerqueira César, 01246903 São Paulo

Head and Neck Surgery Division Heliópolis Hospital Complex, Rua Cônego Xavier 276, Sacomã, 04231-030 São Paulo

Department of Head and Neck Surgery Arnaldo Vieira de Carvalho Cancer Institute, Rua Dr Cesário Motta Junior 112, Vila Buarque, 01221020 São Paulo

Department of Molecular Biology São José do Rio Preto School of Medicine, Av. Brigadeiro Faria Lima 5416-Vila São Pedro, 15090-000 São José do Rio Preto

Department of Genetics and Evolutionary Biology Institute of Biosciences University of São Paulo, R. do Matão, travessa 14 321, Cidade Universitária, 05508-090 São Paulo

Department of Genetics Biosciences Institute University of São Paulo, Rua do Matão, trav. 14 321, Cidade Universitária, 05508-090 São Paulo

School of Medicine USP, São Paulo

Albert Einstein Jewish Teaching and Research Institute (IIEP), São Paulo

School of Medicine of São José do Rio Preto

São José Dos Campos Dental School UNESP

Cancer Institute Arnaldo Vieira de Carvalho, São Paulo

School of Dentistry USP, São Paulo

Heliópolis Hospital, São Paulo

School of Medicine of Ribeirão Preto USP

School of Public Health USP, São Paulo

University of Vale do Paraíba, São José dos Campos

School of Medicine UNIFESP, São Paulo

Faculty of Pharmaceutical Sciences of Ribeirão Preto USP, SP

São José Dos Campos Dental School UNESP

Document Type Journal article
Language English
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