Article
Toxicoproteomics disclose pesticides as downregulators of TNF-a, IL-1b and estrogen receptor pathways in breast cancer women chronically exposed
Registro en:
PIZZATTI, Luciana et al. Toxicoproteomics disclose pesticides as downregulators of TNF-a, IL-1b and estrogen receptor pathways in Breast Cancer women chronically exposed. Frontiers in Oncology. v. 10, n. 1698, p. 1-11, 2020.
2234-943X
10.3389/fonc.2020.01698
2234-943X
Autor
Pizzatti, Luciana
Kawassaki, Aedra Carla Bufalo
Fadel, Bruna
Nogueira, Fabio C. S.
Evaristo, Joseph A. M.
Woldmar, Nicole
Teixeira, Géssica Tuani
Silva, Janaína Carla da
Scandolara, Thalita Basso
Rech, Daniel
Candiotto, Luciano Pessôa Zanetti
Silveira, Guilherme Ferreira
Pavanelli, Wander Rogério
Panis, Carolina
Resumen
Deleterious effects have been widely associated with chronic pesticide exposure, including cancer development. In spite of several known consequences that pesticides can trigger in the human body, few is known regarding its impact on breast câncer women that are chronically exposed to such substances during agricultural work lifelong. In this context, the present study performed a high-throughput toxicoproteomic study in association with a bioinformatics-based design to explore new putative processes and pathways deregulated by chronic pesticide exposure in breast câncer patients. To reach this goal, we analyzed comparatively non-depleted plasma samples from exposed (n = 130) and non-occupationally exposed (n = 112) women diagnosed with breast cancer by using a label-free proteomic tool. The list of proteins differentially expressed was explored by bioinformatics and the main pathways and processes further investigated. The toxicoproteomic study revealed that women exposed to pesticides exhibited mainly downregulated events, linked to immune response, coagulation and estrogen-mediated events in relation to the unexposed ones. Further investigation shown that the identified deregulated processes and pathways correlated with significant distinct levels tumor necrosis factor alpha and interleukin 1 beta in the blood, and specific clinicopathological characteristics pointed out by bioinformatics analysis as adipose-trophic levels, menopause and intratumoral clots formation. Altogether, these findings reinforce pesticides as downregulators of several biological process and highlight that these compounds can be linked to poor prognosis in breast câncer.