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

Rodini,Camila   Oliveira; Xavier,Flávia  Caló Aquino; Paiva,Katiúcia   Batista Silva; De Souza Setúbal Destro,Maria   Fernanda; Moyses,Raquel   Ajub; Michaluarte,Pedro; Carvalho,Marcos   Brasilino; Fukuyama,Erica   Erina; Gencapo,Head and Neck Genome Project; Tajara,Eloiza   Helena; Okamoto,Oswaldo   Keith; Nunes,Fabio   Daumas

doi:10.3892/ijo.2011.1321

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

Authors:
- Camila Oliveira Rodini
- Flávia Caló Aquino Xavier
- Katiúcia Batista Silva Paiva
- Maria Fernanda De Souza Setúbal Destro
- Raquel Ajub Moyses
- Pedro Michaluarte
- Marcos Brasilino Carvalho
- Erica Erina Fukuyama
- Head and Neck Genome Project Gencapo
- Eloiza Helena Tajara
- Oswaldo Keith Okamoto
- Fabio Daumas Nunes
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Affiliations: Laboratory of Molecular Pathology, Department of Oral Pathology, School of Dentistry, University of São Paulo, Cidade Universitária, 05508-000 São Paulo, Brazil , Department of Head and Neck Surgery, School of Medicine, University of São Paulo, Cerqueira César, 01246903 São Paulo, Brazil, Head and Neck Surgery Division, Heliópolis Hospital Complex, Sacomã, 04231-030 São Paulo, Brazil, Department of Head and Neck Surgery, Arnaldo Vieira de Carvalho Cancer Institute, Vila Buarque, 01221020 São Paulo, Brazil, Author list and addresses presented in the Appendix, Department of Molecular Biology, São José do Rio Preto School of Medicine, Vila São Pedro, 15090-000 São José do Rio Preto, Brazil, Human Genome Research Center, Department of Genetics, Biosciences Institute, University of São Paulo, Cidade Universitária, 05508-090 São Paulo, Brazil
Published online on: December 29, 2011 https://doi.org/10.3892/ijo.2011.1321
Pages: 1180-1188

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Abstract

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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