Investigação de biomarcadores presentes em diferentes graus de meningioma por análises metabolômicas
Carregando...
Data
2021-10-19
Autores
Kurokawa, Gabriel Araujo
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
Os meningiomas representam o tipo de tumor primário intracraniano mais comum,
abrangendo cerca de 36% dos casos. São classificados pela Organização Mundial da Saúde em
tumores graus I, II ou III de acordo com seu grau de malignidade. O presente estudo foi
realizado com o intuito de identificar biomarcadores para meningioma, bem como possíveis
marcadores que indiquem progressão do tumor, através da metabolômica exploratória ou sem
alvo específico. Foram selecionadas amostras de sangue de 51 pacientes portadores de
meningioma. Após a extração dos metabólitos, as amostras foram injetadas no equipamento
ESI-LTQ para identificação e seleção de possíveis biomarcadores. As amostras foram
submetidas a análise estatística utilizando a plataforma MetaboAnalyst 5.0 para seleção dos
marcadores diferenciais entre os graus de meningioma. A significância estatística dos
marcadores selecionados foi confirmada através do gráfico Volcano Plot. De acordo com os
valores de massa/carga (m/z) obtidos, as moléculas foram identificadas através da busca em
bancos de dados de metabólitos e pesquisa na literatura científica. Dessa forma, os metabólitos
selecionados como característicos para meningiomas de alto grau, cuja presença está associada
a um prognóstico desfavorável, incluem tirosina (m/z 294), sulfatídeo (m/z 908),
fosfatidilserinas (m/z 800 e 910) e lactosilceramida (m/z 985), possivelmente atuando na
inibição da resposta imune e favorecimento do crescimento celular. Já os marcadores para
meningiomas de baixo grau, cuja presença está associada a benignidade, correspondem a
fosfatidiletanolamina (m/z 710) e diacilglicerol (m/z 577). A identificação das possíveis
identidades de marcadores diferenciais para meningiomas visa o desenvolvimento de um
método diagnóstico assertivo, de baixo custo, capaz de identificar o tumor em seus estágios
iniciais e antever a possibilidade da progressão da doença para estágios malignos, garantindo
um melhor prognóstico ao paciente.
Meningiomas are the most common intracranial tumors embracing 36% of these tumors. According to the World Health Organization (WHO) meningiomas are histologically classified as: I) Low Grade meningiomas (Grade I); and II) High Grade meningiomas (Grade II and III), with Grade I meningiomas being benign tumors while Grade III meningiomas are anaplastic malignant tumors. Since the gold-standard diagnostic methods to detect meningiomas are unable to detect these tumors in its early development stages, the identification of possible differential biomarkers to meningiomas is aimed to develop low-cost, assertive diagnostic methods able to identify the tumor in its early stages of development. To identify possible differential biomarkers for meningioma capable to differ Low Grade from High Grade tumors through metabolomics analysis. Plasma samples from 51 patients were collected. Within those patients, 43 were Grade I, 5 were Grade II and 3 were Grade III meningioma patients. The metabolites from their plasma were extracted, ionized and injected in mass spectrometer. According to the obtained mass/charge values, the molecules were identified through search in the metabolites databases (METLIN, HMDB and LIPID MAPS) and the scientific literatures. The High Grade meningioma selected biomarkers includ O-Benzyl-L-Tyrosine (m/z 294), 3-O-Sulfogalactosylceramide (m/z 908), phosphatidylserine (m/z 800 and 910) and lactosylceramide (m/z 985), while the Low Grade meningioma biomarkers correspond to phosphatidylethanolamine (m/z 710) and diacylglycerol (m/z 577). The selected biomarkers statistical significance was assured by the Volcano Plot, and the accuracy of our method was confirmed through the ROC curve (AUC = 0,957). The identification of the possible differential biomarkers to meningiomas through metabolomics analysis aims to develop low-cost, assertive diagnostic methods able to identify the tumor in its early stages of development and to anticipate the disease progression to malignant stages, so ensuring a better prognostic to the patient.
Meningiomas are the most common intracranial tumors embracing 36% of these tumors. According to the World Health Organization (WHO) meningiomas are histologically classified as: I) Low Grade meningiomas (Grade I); and II) High Grade meningiomas (Grade II and III), with Grade I meningiomas being benign tumors while Grade III meningiomas are anaplastic malignant tumors. Since the gold-standard diagnostic methods to detect meningiomas are unable to detect these tumors in its early development stages, the identification of possible differential biomarkers to meningiomas is aimed to develop low-cost, assertive diagnostic methods able to identify the tumor in its early stages of development. To identify possible differential biomarkers for meningioma capable to differ Low Grade from High Grade tumors through metabolomics analysis. Plasma samples from 51 patients were collected. Within those patients, 43 were Grade I, 5 were Grade II and 3 were Grade III meningioma patients. The metabolites from their plasma were extracted, ionized and injected in mass spectrometer. According to the obtained mass/charge values, the molecules were identified through search in the metabolites databases (METLIN, HMDB and LIPID MAPS) and the scientific literatures. The High Grade meningioma selected biomarkers includ O-Benzyl-L-Tyrosine (m/z 294), 3-O-Sulfogalactosylceramide (m/z 908), phosphatidylserine (m/z 800 and 910) and lactosylceramide (m/z 985), while the Low Grade meningioma biomarkers correspond to phosphatidylethanolamine (m/z 710) and diacylglycerol (m/z 577). The selected biomarkers statistical significance was assured by the Volcano Plot, and the accuracy of our method was confirmed through the ROC curve (AUC = 0,957). The identification of the possible differential biomarkers to meningiomas through metabolomics analysis aims to develop low-cost, assertive diagnostic methods able to identify the tumor in its early stages of development and to anticipate the disease progression to malignant stages, so ensuring a better prognostic to the patient.
Descrição
Palavras-chave
Meningioma, Metabolômica, Biomarcadores, Metabolomics, Biomarkers