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

Autor(es):Mostrar menos -

Rodini, Camila Oliveira ; Aquino Xavier, Flavia Calo ; Silva Paiva, Katiucia Batista ; De Souza Setubal Destro, Maria Fernanda ; Moyses, Raquel Ajub ^[1] ; Michaluarte, Pedro ^[1] ; Carvalho, Marcos Brasilino ^[2] ; Fukuyama, Erica Erina ^[3] ; Tajara, Eloiza Helena ^{[4, 5]} ; Okamoto, Oswaldo Keith ^[6] ; Nunes, Fabio Daumas ^[7] ; Gencapo, Head Neck Genome Project

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Dept Head & Neck Surg, BR-01246903 Sao Paulo - Brazil

^[2] Heliopolis Hosp Complex, Div Head & Neck Surg, BR-04231030 Sao Paulo - Brazil

^[3] Arnaldo Vieira da Carvalho Canc Inst, Dept Head & Neck Surg, BR-01221020 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Biosci, Dept Genet & Evolutionary Biol, BR-05508090 Sao Paulo - Brazil

^[5] Sao Jose do Rio Preto Sch Med, Dept Mol Biol, BR-15090000 Sao Jose Do Rio Preto - Brazil

^[6] Univ Sao Paulo, Biosci Inst, Dept Genet, Human Genome Res Ctr, BR-05508090 Sao Paulo - Brazil

^[7] Univ Sao Paulo, Fac Odontol, Sch Dent, Dept Oral Pathol, Lab Mol Pathol, BR-05508000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Oncology; v. 40, n. 4, p. 1180-1188, APR 2012.
• Citações Web of Science: 18

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. (AU)

• Processo FAPESP: 04/14029-1 - Obtenção de biomarcadores e identificação de alvos terapêuticos em tumores por estudo de expressão gênica
• Beneficiário: Carlos Alberto Moreira Filho
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 04/12054-9 - Busca de marcadores de agressividade em tumores de cabeça e pescoço
• Beneficiário: Eloiza Helena Tajara da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Temático