Integrative analysis of the prostate proteome of rats exposed to a phthalate mixture in the perinatal period associated with the human secretome: Potential biomarkers of toxicity and oncogenesis

Abstract

The prostate gland is extremely important for the male reproductive system and is increasingly gaining prominence due to the high incidence of Prostate Cancer (PCa). Phthalates are a group of chemical compounds used as plasticizers to confer greater malleability and flexibility and are considered Endocrine Disruptors (ED) due to their antiandrogenic action. Previous work from our research group has demonstrated that gestational and lactational exposure to phthalates alters the expression pattern of genes and miRNAs in the rat prostate related to oncogenesis. In this sense, the aim of this study will be to determine through an in silico study, from the proteomic analysis of the prostate of rats exposed to a mixture of phthalates, the main secreted proteins and align these data with human secretome database in patients with prostate cancer, aiming to establish similarity parameters, and map possible molecules that may serve as markers of toxicity and oncogenesis. To this end, Differentially expressed proteins in the proteome of mice exposed to phthalates during perinatal development (gestation and lactation) will be compared to predicted secreted protein profile data in humans available in "The human protein Atlas" platform. The proteins obtained in the previous analysis, will be analyzed according to their interaction by the protein-protein interaction network, obtained in the String platform and the KOBAS 3.0 platform, aiming to obtain the enrichment analyses that point out pathways and ontological terms modulated by the differentially expressed proteins. After that, the data will be crossed with data for prostate adenocarcinoma on the HPA platform and "The Cancer Genome Atlas" (TCGA) platform, in addition to establishing the survival ratio when the selected targets are differentially expressed. Finally, the targets found will be validated by RT-qPCR.