C Panis1,2, R Binato3, S Correa3, V J Victorino4,5, V Dias-Alves4, A C S A Herrera6, R Cecchini7, A N C Simão8, D S Barbosa8, L Pizzatti9, E Abdelhay3. 1. Laboratório de Células Tronco, Instituto Nacional de Câncer, INCA, Rio De Janeiro, Brazil. carolpanis@hotmail.com. 2. Laboratório de Mediadores Inflamatórios, Programa de Pós-Graduação em Ciências Aplicadas à Saúde, Universidade Estadual do Oeste do Paraná, UNIOESTE, Campus Francisco Beltrão, Rua Maringá, 1200, Vila Nova, Francisco Beltrão, Paraná, Brazil. carolpanis@hotmail.com. 3. Laboratório de Células Tronco, Instituto Nacional de Câncer, INCA, Rio De Janeiro, Brazil. 4. Laboratório de Mediadores Inflamatórios, Programa de Pós-Graduação em Ciências Aplicadas à Saúde, Universidade Estadual do Oeste do Paraná, UNIOESTE, Campus Francisco Beltrão, Rua Maringá, 1200, Vila Nova, Francisco Beltrão, Paraná, Brazil. 5. Laboratório de Imunopatologia, Universidade Estadual de Londrina, Londrina, Paraná, Brazil. 6. Pontifícia Universidade Católica, PUC, Campus Londrina, Londrina, Paraná, Brazil. 7. Laboratório de Fisiopatologia e Radicais Livres, Universidade Estadual de Londrina, Londrina, Paraná, Brazil. 8. Departamento de Patologia, Toxicologia e Análises Clínicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil. 9. Laboratório de Biologia Molecular e Proteômica do Sangue, LABMOPS, Universidade Federal do Rio de Janeiro, Rio De Janeiro, Brazil.
Abstract
PURPOSE: Although paclitaxel-based chemotherapy is widely used for treating breast cancer, paclitaxel therapy has been associated with several adverse effects. Such adverse effects have primarily been associated with long-term regimens, but some acute effects are being increasingly reported in the literature. In this context, the present study analyzed the systemic proteomic profiles of women diagnosed with breast cancer at the first cycle of short paclitaxel infusion (n = 30). Proteomic profiles thus obtained were compared with those of breast cancer patients without chemotherapy (n = 50), as well as with those of healthy controls (n = 40). METHODS: Plasma samples were evaluated by label-free LC-MS to obtain systemic proteomic profiles. Putative dysregulated pathways were identified and validated by in silico analysis of proteomic profiles. RESULTS: Our results identified 188 proteins that were differentially expressed in patients who received a single short paclitaxel infusion when compared to patients who did not receive the infusion. Gene ontology analysis indicated that the cholesterol pathway may be dysregulated by paclitaxel in these patients. Validation analysis showed that paclitaxel treatment significantly reduced plasma high-density lipoprotein levels and increased plasma hydroperoxide levels when compared to breast cancer patients without chemotherapy. Furthermore, augmented C-reactive protein and creatine kinase fraction MB were found to be significantly higher in paclitaxel-treated patients in comparison with healthy controls. CONCLUSIONS: Taken together, these data suggest that a single dose of short paclitaxel infusion is sufficient to trigger significant alterations in lipid metabolism, which puts breast cancer patients at risk for increased incidence of cardiovascular disease.
PURPOSE: Although paclitaxel-based chemotherapy is widely used for treating breast cancer, paclitaxel therapy has been associated with several adverse effects. Such adverse effects have primarily been associated with long-term regimens, but some acute effects are being increasingly reported in the literature. In this context, the present study analyzed the systemic proteomic profiles of women diagnosed with breast cancer at the first cycle of short paclitaxel infusion (n = 30). Proteomic profiles thus obtained were compared with those of breast cancerpatients without chemotherapy (n = 50), as well as with those of healthy controls (n = 40). METHODS: Plasma samples were evaluated by label-free LC-MS to obtain systemic proteomic profiles. Putative dysregulated pathways were identified and validated by in silico analysis of proteomic profiles. RESULTS: Our results identified 188 proteins that were differentially expressed in patients who received a single short paclitaxel infusion when compared to patients who did not receive the infusion. Gene ontology analysis indicated that the cholesterol pathway may be dysregulated by paclitaxel in these patients. Validation analysis showed that paclitaxel treatment significantly reduced plasma high-density lipoprotein levels and increased plasma hydroperoxide levels when compared to breast cancerpatients without chemotherapy. Furthermore, augmented C-reactive protein and creatine kinase fraction MB were found to be significantly higher in paclitaxel-treated patients in comparison with healthy controls. CONCLUSIONS: Taken together, these data suggest that a single dose of short paclitaxel infusion is sufficient to trigger significant alterations in lipid metabolism, which puts breast cancerpatients at risk for increased incidence of cardiovascular disease.
Entities:
Keywords:
Breast cancer; Cholesterol metabolism; Lipids; Proteomics
Authors: Bruno R B Pires; Carolina Panis; Vinícius Dias Alves; Ana C S A Herrera; Renata Binato; Luciana Pizzatti; Rubens Cecchini; Eliana Abdelhay Journal: Oxid Med Cell Longev Date: 2019-08-08 Impact factor: 6.543