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

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2012-04-01

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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

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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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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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International Journal of Oncology, v. 40, n. 4, p. 1180-1188, 2012.

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