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Toxicoproteomics Disclose Pesticides as Downregulators of TNF-α, IL-1β and Estrogen Receptor Pathways in Breast Cancer Women Chronically Exposed

Authors: Janaína Carla da Silva; Aedra Carla Bufalo Kawassaki; Luciano Pessôa Zanetti Candiotto; Fábio C. S. Nogueira; Géssica Tuani Teixeira; Nicole Woldmar; Guilherme Ferreira Silveira; +9 Authors

Toxicoproteomics Disclose Pesticides as Downregulators of TNF-α, IL-1β and Estrogen Receptor Pathways in Breast Cancer Women Chronically Exposed

Abstract

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 cancer 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 cancer 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 cancer.

Keywords

interleukin beta 1, breast cancer, Oncology, toxicoproteomics, tumor necrosis factor alfa, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, estrogen signaling, RC254-282

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
22
Top 10%
Average
Top 10%
Green
gold