Avaliação da expressão gênica da proteína 2 ligante de SH3 ativadora da GTPase de Ras (G3BP2), do fator da tecidual (TF) e da isoforma asHTF como possíveis marcadores prognósticos em carcinoma epidermóide de cabeça e pescoço / Evaluation of gene expression GTPase activating protein (SH3 domain) binding protein 2 (G3BP2), tissue factor (TF) and its isoform asHTF as possible prognostic markers in head and neck squamous cell carcinoma
AUTOR(ES)
Lilian Pires Barbeta
DATA DE PUBLICAÇÃO
2009
RESUMO
GTPase activating protein (SH3 domain) binding protein 2 (G3BP2) seems to be involved in pathways important for cell survival as NF- B pathway. Tissue factor (TF) and its isoform asHTF appear to be involved in angiogenesis, proliferation and metastasis. Thus, the genes G3BP2, TF and asHTF seem possible prognostic factors in head and neck squamous cell carcinoma (SCC). To assess the importance of these genes in this type of cancer, we performed mRNA expression analysis of these markers by real time PCR (polymerase chain reaction) in primary tumors and adjacent mucosa of 148 patients with oral cavity, tongue and larynx SCC. TF and asHTF protein was determined by Western blotting in 17 patients with oral cavity SCC. mRNA expression levels were correlated with clinical and pathological variables and survival of patients. G3BP2 mRNA expression was lower in primary tumors as compared to adjacent mucosa at all sites analyzed. No difference was found between TF and asHTF expression in primary tumors and adjacent mucosa in the whole group. TF and asHTF levels mRNA expression were higher in pN+ tumors as compared to pN0 in oral cavity (P=0.003, P = 0.004, respectively) and tongue (P= 0.033, P= 0.018, respectively - Mann-Whitney test) tumors. For Kaplan Meier survival analysis patients were categorized positive (expression >tumor median relative expression) and negative (expression tumor median relative expression). For oral cavity SCC, patients with positive expression of TF (P =0.034 - log-rank test) and asHTF (P =0.010) genes presented shorter disease-free survival in univariate analysis. In multivariate analysis both TF as asHTF retained statistical significance (P=0.002 for both genes), suggesting, therefore, are independent prognostic factors. Protein analysis showed 76.4% agreement with mRNA expression for TF and 58.8% for asHTF. In patients with tongue and larynx tumors there correlation were not found. Thus, we suggest that the TF and asHTF expression seem to be prognostic markers in oral cavity SCC especially in relation to disease-free survival. Supported by FAPESP 06/53755-5
ASSUNTO(S)
neoplasias de cabeça e pescoço thrombosplastin gene expression survivorship (public health) expressão gênica squamous cell tromboplastina carcinoma de células escamosas carcinoma head and neck neoplasm sobrevida
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