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

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 gen...

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Detalhes bibliográficos
Autores: 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., 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.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2012
País:Brasil
Recursos:Universidade Estadual Paulista (UNESP)
Repositorio:Repositório Institucional da UNESP
Idioma:inglés
OAI Identifier:oai:repositorio.unesp.br:11449/73253
Acesso em linha:http://dx.doi.org/10.3892/ijo.2011.1321
http://hdl.handle.net/11449/73253
Access Level:acceso abierto
Palavra-chave: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
Descrição
Resumo: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.

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