Busca de potenciais biomarcadores para leucoplasia verrucosa proliferativa
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Data
2022-01-20
Autores
Arroyo Ormeño, Esteban Alexis
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
O carcinoma espinocelular (CEC) representa mais de 95% de todas as neoplasias malignas que acometem a cavidade oral e muitas vezes estes tumores são precedidos por alterações clínicas que apresentam um evidente potencial de transformação maligna, as quais são chamadas de desordens potencialmente malignas orais (DPMO). Dentre estas, a leucoplasia oral (LO) é a mais importante das DPMOs com uma de incidência de 3,4% e uma taxa de transformação maligna que varia de 0,2% até 17,5%. Uma forma menos reconhecida e ainda pouco compreendida de leucoplasia, denominada leucoplasia verrucosa proliferativa (LVP), representa uma variante de comportamento persistente e progressivo para malignidade, com uma taxa de transformação maligna maior que 70%. O diagnóstico da LVP atualmente só́ é possível por meio da observação temporal e individual de cada paciente, com a demonstração de progressão clínica e histológica das lesões para um CEC. No entanto, ainda não existem métodos moleculares ou biomarcadores que possam de forma confiável auxiliar no diagnóstico diferencial e precoce entre LO e LVP. Além disto, a LVP frequentemente apresenta resposta inadequada a todas as modalidades de tratamento e sofre altas taxas de recidiva. Diante disto, identificar potenciais biomarcadores para LVP poderá́ auxiliar no diagnóstico diferencial, prognóstico e tratamento desta DPMO. Assim, a principal hipótese deste projeto é: O perfil proteômico entre LO e LVP é distinto e a sua caracterização poderá́ auxiliar no entendimento do comportamento clínico distinto entre estas DPMOs. Para testar esta hipótese, os objetivos específicos deste estudo consistem em (1) identificar potenciais biomarcadores por meio da associação da microdissecção a laser (ML) e espectrometria de massas em tandem (MS/MS); (2) avaliar possíveis mecanismos biológicos associados aos principais biomarcadores identificados por meio de ferramentas bioinformáticas e; (3) realizar estudos de validação in vitro.
Oral squamous cell carcinoma (OSCC) represents more than 95% of all malignant neoplasms in the oral cavity and often these tumours are preceded by clinical entities which have a clear potential for malignant transformation, these are so-called oral potentially malignant disorders (OPMD). Among these, oral leukoplakia (OL) is the most prevalent OPMD with an incidence of 3.4% and a malignant transformation rate ranging from 0.2% to 17.5%. A less recognised and still poorly understood form of OL, is the proliferative verrucous leukoplakia (PVL), which represents a variant of recalcitrant and progressive behaviour towards malignancy, with a malignant transformation rate higher than 70%. Currently, the diagnosis of PVL is only based on the temporal and individual observation, with demonstration of clinical and histological progression of these lesions to OSCC. Regardless, there are still no molecular methods or biomarkers that can reliably assist in the differential and early diagnosis between OL and PVL. Moreover, PVL often shows an inadequate response to all treatment modalities and suffers high rates of recurrence. Therefore, identifying potential biomarkers for PLV may help in the differential diagnosis, prognosis and treatment of this OPMD. Thus, the main hypothesis of this research is: The proteomic profile between LO and LVP is different and its characterization may help in the understanding of the distinct clinical behaviour between these OPMD. To prove this, the main goals of this study are (1) identify potential biomarkers through the association of laser microdissection (LM) and mass spectrometry in tandem (MS/MS); (2) assess possible biological mechanisms associated with the main biomarkers founded by the aid of bioinformatics tools and; (3) performing in vitro validation assays.
Oral squamous cell carcinoma (OSCC) represents more than 95% of all malignant neoplasms in the oral cavity and often these tumours are preceded by clinical entities which have a clear potential for malignant transformation, these are so-called oral potentially malignant disorders (OPMD). Among these, oral leukoplakia (OL) is the most prevalent OPMD with an incidence of 3.4% and a malignant transformation rate ranging from 0.2% to 17.5%. A less recognised and still poorly understood form of OL, is the proliferative verrucous leukoplakia (PVL), which represents a variant of recalcitrant and progressive behaviour towards malignancy, with a malignant transformation rate higher than 70%. Currently, the diagnosis of PVL is only based on the temporal and individual observation, with demonstration of clinical and histological progression of these lesions to OSCC. Regardless, there are still no molecular methods or biomarkers that can reliably assist in the differential and early diagnosis between OL and PVL. Moreover, PVL often shows an inadequate response to all treatment modalities and suffers high rates of recurrence. Therefore, identifying potential biomarkers for PLV may help in the differential diagnosis, prognosis and treatment of this OPMD. Thus, the main hypothesis of this research is: The proteomic profile between LO and LVP is different and its characterization may help in the understanding of the distinct clinical behaviour between these OPMD. To prove this, the main goals of this study are (1) identify potential biomarkers through the association of laser microdissection (LM) and mass spectrometry in tandem (MS/MS); (2) assess possible biological mechanisms associated with the main biomarkers founded by the aid of bioinformatics tools and; (3) performing in vitro validation assays.
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Palavras-chave
Leucoplasia oral, Proteômica, Biomarcadores, Oral leukoplakia, Proteomics, Biomarkers