Influência da via hippo em carcinomas de células escamosas de língua oral
Oral tongue squamous cell carcinoma (OTSCC) has high morbidity and mortality rates. Despite the progress made in this area, researchers continue to search for molecular biomarkers that have predictive value in the prognosis of patients and allow the development of new therapeutic strategies. In t...
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Formato: | doctoralThesis |
Idioma: | pt_BR |
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Universidade Federal do Rio Grande do Norte
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Endereço do item: | https://repositorio.ufrn.br/handle/123456789/51987 |
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Resumo: | Oral tongue squamous cell carcinoma (OTSCC) has high morbidity and mortality rates.
Despite the progress made in this area, researchers continue to search for molecular
biomarkers that have predictive value in the prognosis of patients and allow the
development of new therapeutic strategies. In this context, several studies have
highlighted the role of the Hippo pathway for this purpose. Therefore, this research
aimed to evaluate whether the proteins related to the Hippo pathway, LATS2 and
YAP1, have some influence on the OTSCC biological behavior. The sample consisted
of 26 OTSCC cases and 8 normal oral mucosa cases as control. For the morphological
assessment of OTSCC, the gradations proposed by the WHO (2005) and by Almangush
et al. (2014) were performed. The immunohistochemical profile of LATS2 and YAP1
was evaluated by scores (0-3), based on their immunoexpression in intracellular
location (nucleus and/or cytoplasm) and epithelial distribution. Pearson's Chi-square
and Fisher's Exact statistical tests were performed for the analysis of the studied
parameters. Survival analysis was performed using the Kaplan-Meier method and the
log-rank test. For all evaluations, values with p<0.05 were considered significant. High
expression of LATS2 was observed both in normal oral mucosa (100%) and in most
OTSCC (73,1%), with no statistically significant difference (p=0,160). It was possible
to observe the increase in YAP immunoexpression in cases of OTSCC compared to the
normal oral mucosa (p<0.001). It was also found that the LATS2 low expression was
associated with lower rates of disease-free survival (p=0.039). Furthermore, YAP high
expression was found associated with the BD model's high-risk classification (p=0.034),
suggesting this protein immunoexpression may be associated with EMT and cell
invasion in OTSCC. The high expression of both proteins in most OTSCC suggests that
other signaling pathways, in addition to regulating through LATS2, may be inducing the
nuclear YAP expression in these tumors. Therefore, it is concluded that the Hippo
pathway can influence the OTSCC biological behavior. |
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