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Doctoral Thesis
DOI
10.11606/T.23.2009.tde-08042009-112014
Document
Author
Full name
Camila de Oliveira Rodini
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Nunes, Fabio Daumas (President)
Carvalho, Marcos Brasilino de
Federico, Miriam Hatsue Honda
Okamoto, Oswaldo Keith
Severino, Patrícia
Title in Portuguese
Expressão de transcritos de genes homeobox no carcinoma epidermóide de boca: análise por microarray, validação por qRT-PCR e relação com critérios clínicos de agressividade
Keywords in Portuguese
Carcinoma epidermóide de boca
Genes homeobox
qRT-PCR
Abstract in Portuguese
A busca de marcadores moleculares para o refinamento diagnóstico, classificação e estabelecimento do prognóstico dos tumores, e individualização terapêutica tem sido foco de várias pesquisas. O presente estudo teve como objetivo investigar, em carcinoma epidermóide de língua e/ou assoalho bucal, a presença de transcritos dos genes homeobox que pudessem se revelar marcadores moleculares de prognóstico e/ou agressividade tumoral. Após análise por microarray utilizando-se amostras de tumores e margens classificados como mais e menos agressivos, os genes homeobox HOXC13, HOXD10, HOXD11, IRX4, PROX1 e ZHX1 foram selecionados e sua hiper-expressão foi parcialmente validada por qRT-PCR. Observou-se aumento da expressão de HOXD10, HOXD11 e IRX4 em tumores com relação às margens correspondentes, bem como nos tumores menos agressivos em relação às suas respectivas margens. Por outro lado, os genes PROX1 e ZHX1 estavam mais expressos nas margens que nos tumores correspondentes. Esses resultados sugerem que a expressão alterada de HOXD10, HOXD11 e IRX4 pode participar no desenvolvimento do carcinoma epidermóide de língua e/ou assoalho bucal, enquanto os genes PROX1 e ZHX1 provavelmente exibem perda de função ou estão silenciados na neoplasia. Houve uma tendência de associação entre a expressão elevada de HOXD11 e presença de infiltrações linfática e perineural, e grau moderado de diferenciação da neoplasia, bem como entre a expressão elevada de HOXD10 e infiltração linfática. O gene IXR4 foi relacionado com um menor tempo de sobrevida global. Não foi possível estabelecer, dentre os genes homeobox validados por qRT-PCR, um gene ou uma combinação deles que pudesse(m) ser utilizado(s) como marcador(es) de agressividade tumoral.
Title in English
Homeobox genes transcripts expression in oral squamous cell carcinoma: microarray analysis, qRT-PCR validation and association with clinical criteria of aggressiveness
Keywords in English
Homeobox Genes
Oral squamous cell carcinoma
qRT-PCR
Abstract in English
The search for molecular markers to diagnosis improvement, treatment individualization and establishment of oral squamous cell carcinoma prognosis has been the focus of several studies. The present study investigated the presence of specific transcript of homeobox genes in squamous cell carcinoma of the tongue and/or floor of the mouth that might reflect relevant molecular markers of prognosis and/or tumor aggressiveness. After microarray analysis of tumor samples classified as more or less aggressive, and non tumoral margins, HOXC13, HOXD10, HOXD11, IRX4, PROX1 and ZHX1 selected and partially validated by qRT-PCR. Increased expression of HOXD10, HOXD11, IRX4 in tumors in comparison to margins as well as in less aggressive tumors related to their margins was observed. On the other hand, a decreased expression of PROX1 and ZHX1 was observed in margins compared to their respective tumors. These results suggest that the altered expression of HOXD10, HOXD11 and IRX4 may participate in the development of squamous cell carcinoma of the tongue and/or floor of the mouth, while PROX1 and ZHX1 probably present loss of function or are silenced in tumors. A tendency of association between increased expression of HOXD11 and lymphatic and perineural infiltration, as well as moderately differentiated tumors, and increased expression of HOXD10 and lymphatic infiltration was observed. Still, increased expression of IRX4 may apparently influence global survival rate. However, the results of the present study must be confirmed in a greater number of samples, and complemented with the evaluation of HOXD10, HOXD11, IRX4 protein levels. It was not possible to establish, among homeobox genes validated through qRT-PCR, a gene or a combination of genes capable of predicting tumor aggressiveness.
 
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CAMILADEOLIVEIRARODINI.pdf (1,005.00 Kbytes)
Publishing Date
2009-06-08
 
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