Comparação dos níveis séricos de citocinas, quimiocinas e micropartículas em mulheres com câncer de mama e de ovário
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Data
2017-11-24
Autores
Santiago, Aline Evangelista
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Universidade Estadual Paulista (Unesp)
Resumo
Introdução: A concentração plasmática de citocinas, quimiocinas e micropartículas (MPs) em mulheres com câncer de mama e de ovário é uma forma não invasiva de avaliar a resposta inflamatória/regulatória sistêmica associada a esses tumores e o papel do microambiente formado na resposta pró e antitumoral na paciente. Portanto, o objetivo deste estudo foi comparar o perfil da resposta inflamatória sistêmica do câncer epitelial de ovário (CEO) e do câncer de mama através da medição de citocinas, quimiocinas e MPs, para assim avaliar se existe ou não diferença nesse padrão de resposta inflamatória sistêmica. Métodos: Noventa e quatro mulheres sem evidência de malignidade (n = 30), com câncer de mama (n = 38) ou câncer de ovário epitelial (n = 26) foram avaliadas. Foram coletadas amostras plasmáticas e de tecido tumoral. A avaliação dos marcadores inflamatórios foi realizada pela dosagem de citocinas (IL-1, IL-2, IL-6, IL-10, IL-12, IL-17A, TNF-α e IFN- ), quimiocinas (CXCL8, CXCL -9, CXCL 10, CCL 2, CCL5) e MPs (neutrófilos, leucócitos, monócitos, eritrócitos, células endoteliais, plaquetas e linfócitos) por citometria de fluxo / Cytometric Bead Array. As diferenças entre os grupos foram avaliadas por Kruskal-Wallis. As diferenças com p<0,05 foram consideradas significantes. Resultados: Os níveis plasmáticos das citocinas pró-inflamatórias IL-6 (p=<0,001), TNF-α (p=0,004) e IL-12 (p=0,0019) foram significativamente maiores em pacientes com câncer de ovário em comparação com as mulheres com câncer de mama e com o grupo controle. Pacientes com câncer de ovário foram também associadas a maiores níveis de IL-10 (p<0,001) e das quimiocinas CXCL-9 (p<0,001) e CXCL-10 (p<0,001) em comparação aos outros grupos. Os níveis de MPs derivados de neutrófilos aumentaram significativamente em amostras plasmáticas de pacientes com CEO em comparação com mulheres com câncer de mama e do grupo controle (p<0,001). Em contraste, as MPs derivadas de células endoteliais foram menores nas pacientes com CEO em comparação com os demais grupos (p=0,0491). Houve um equilíbrio entre citocinas, quimiocinas e MPs nos grupos de câncer de mama e controle. A rede de citocinas e quimiocinas inflamatórias/regulatórias em pacientes com CEO apresentou maior complexidade em relação aos demais grupos e com fortes interações nas redes entre fatores inflamatórios e imunológicos plasmáticos. Esta rede incluiu mais biomarcadores associados com correlações negativas e positivas entre eles. Conclusão: Este estudo é uma pesquisa promissora e original. Os resultados podem refletir as discrepâncias entre a carcinogênese no câncer de ovário e de mama, sugerindo um padrão inflamatório sistêmico maior no CEO. MPs podem servir como uma nova fonte de informação relacionada à doença.
Introduction: The plasma concentration of cytokines, chemokines and microparticles (MPs) in women with breast and ovarian cancer is a noninvasive way of assessing the systemic inflammatory / regulatory response associated with these tumors and the role of the microenvironment formed in the pro and antitumor response in the patient. Therefore, the objective of this study was to compare the profile of the systemic inflammatory response of epithelial ovarian cancer (EOC) and breast cancer by measuring cytokines, chemokines and MPs, in order to evaluate whether or not there is a difference in this pattern of inflammatory response systemic. Methods: Ninety-four women with no evidence of malignancy (n = 30), breast cancer (n = 38) or epithelial ovarian cancer (n = 26) were evaluated. Plasma samples and tumor tissue were collected. The evaluation of inflammatory markers was performed by the measurement of cytokines (IL-1, IL-2, IL-6, IL-10, IL-12, IL-17A, TNF-α and IFN-), chemokines (CXCL8, CXCL -9, CXCL 10, CCL 2, CCL 5) and MPs (neutrophils, leukocytes, monocytes, erythrocytes, endothelial cells, platelets and lymphocytes) by flow cytometry / Cytometric Bead Array. The differences between the groups were assessed by Kruskal-Wallis. Differences with p <0.05 were considered significant. Results: Plasma levels of the proinflammatory cytokines IL-6 (p = 0.001), TNF-α (p = 0.004) and IL-12 (p = 0.0019) were significantly higher in ovarian cancer patients compared to women with breast cancer and the control group. Patients with ovarian cancer were also associated with higher levels of IL-10 (p <0.001) and CXCL-9 (p <0.001) and CXCL-10 (p <0.001) chemokines compared to the other groups. Levels of MPs derived from neutrophils increased significantly in plasma samples of EOC patients compared to women with breast cancer and the control group (p <0.001). In contrast, MPs derived from endothelial cells were lower in patients with EOC compared to the other groups (p = 0.0491). There was a balance between cytokines, chemokines and MPs in the breast cancer and control groups. The network of inflammatory / regulatory cytokines and chemokines in patients with EOC presented greater complexity in relation to the other groups and with strong interactions in the networks between inflammatory and immunological plasmatic factors. This network included more biomarkers associated with negative and positive correlations between them. Conclusion: This study is a promising and original research. The results may reflect the discrepancies between carcinogenesis in ovarian and breast cancer, suggesting a higher systemic inflammatory pattern in the EOC. MPs can serve as a new source of disease-related information.
Introduction: The plasma concentration of cytokines, chemokines and microparticles (MPs) in women with breast and ovarian cancer is a noninvasive way of assessing the systemic inflammatory / regulatory response associated with these tumors and the role of the microenvironment formed in the pro and antitumor response in the patient. Therefore, the objective of this study was to compare the profile of the systemic inflammatory response of epithelial ovarian cancer (EOC) and breast cancer by measuring cytokines, chemokines and MPs, in order to evaluate whether or not there is a difference in this pattern of inflammatory response systemic. Methods: Ninety-four women with no evidence of malignancy (n = 30), breast cancer (n = 38) or epithelial ovarian cancer (n = 26) were evaluated. Plasma samples and tumor tissue were collected. The evaluation of inflammatory markers was performed by the measurement of cytokines (IL-1, IL-2, IL-6, IL-10, IL-12, IL-17A, TNF-α and IFN-), chemokines (CXCL8, CXCL -9, CXCL 10, CCL 2, CCL 5) and MPs (neutrophils, leukocytes, monocytes, erythrocytes, endothelial cells, platelets and lymphocytes) by flow cytometry / Cytometric Bead Array. The differences between the groups were assessed by Kruskal-Wallis. Differences with p <0.05 were considered significant. Results: Plasma levels of the proinflammatory cytokines IL-6 (p = 0.001), TNF-α (p = 0.004) and IL-12 (p = 0.0019) were significantly higher in ovarian cancer patients compared to women with breast cancer and the control group. Patients with ovarian cancer were also associated with higher levels of IL-10 (p <0.001) and CXCL-9 (p <0.001) and CXCL-10 (p <0.001) chemokines compared to the other groups. Levels of MPs derived from neutrophils increased significantly in plasma samples of EOC patients compared to women with breast cancer and the control group (p <0.001). In contrast, MPs derived from endothelial cells were lower in patients with EOC compared to the other groups (p = 0.0491). There was a balance between cytokines, chemokines and MPs in the breast cancer and control groups. The network of inflammatory / regulatory cytokines and chemokines in patients with EOC presented greater complexity in relation to the other groups and with strong interactions in the networks between inflammatory and immunological plasmatic factors. This network included more biomarkers associated with negative and positive correlations between them. Conclusion: This study is a promising and original research. The results may reflect the discrepancies between carcinogenesis in ovarian and breast cancer, suggesting a higher systemic inflammatory pattern in the EOC. MPs can serve as a new source of disease-related information.
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Palavras-chave
câncer de mama, câncer de ovário, citocinas, micropartículas, quimiocinas, breast cancer, chemokines, cytokines, microparticles, ovarian cancer