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DIFFERENTIAL PROTEOMIC COMPARISON OF BREAST CANCER SECRETOME USING A QUANTITATIVE PAIRED ANALYSIS WORKFLOW
Author
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxinologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Proteômica e Engenharia de Proteínas. Curitiba, PR, Brasil.
Universidade Federal do Rio de Janeiro. Programa de Engenharia de Sistemas e Ciência da Computação. Rio de Janeiro, RJ, Brasil.
Instituto Fernandes Figueira. Departamento de Ginecologia. Laboratório de Biologia Molecular Aplicada, Flamengo, RJ, Brasil.
Universidade do Estado do Rio de Janeiro. Departamento de Genética. Laboratório de Biologia Molecular de Tumores, Maracanã, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxinologia. Rio de Janeiro, RJ, Brasil.
Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V, Dortmund, Germany / Segal Cancer Proteomics Centre, Lady Davis Institute at the Jewish General Hospital, McGill University, Montréal, Canada.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxinologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxinologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Proteômica e Engenharia de Proteínas. Curitiba, PR, Brasil.
Universidade Federal do Rio de Janeiro. Programa de Engenharia de Sistemas e Ciência da Computação. Rio de Janeiro, RJ, Brasil.
Instituto Fernandes Figueira. Departamento de Ginecologia. Laboratório de Biologia Molecular Aplicada, Flamengo, RJ, Brasil.
Universidade do Estado do Rio de Janeiro. Departamento de Genética. Laboratório de Biologia Molecular de Tumores, Maracanã, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxinologia. Rio de Janeiro, RJ, Brasil.
Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V, Dortmund, Germany / Segal Cancer Proteomics Centre, Lady Davis Institute at the Jewish General Hospital, McGill University, Montréal, Canada.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxinologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxinologia. Rio de Janeiro, RJ, Brasil.
Abstract
Worldwide, breast cancer is the main cause of cancer mortality in women. Most cases originate in mammary ductal cells that produce the nipple aspirate fluid (NAF). In cancer patients, this secretome contains proteins associated with the tumor microenvironment. NAF studies are challenging because of inter-individual variability. We introduced a paired-proteomic shotgun strategy that relies on NAF analysis from both breasts of patients with unilateral breast cancer and extended PatternLab for Proteomics software to take advantage of this setup. As methods, The software is based on a peptide-centric approach and uses the binomial distribution to attribute a probability for each peptide as being linked to the disease; these probabilities are propagated to a final protein p-value according to the Stouffer’s Z-score method. It's results a total of 1227 proteins were identified and quantified, of which 87 were differentially abundant, being mainly involved in glycolysis (Warburg effect) and immune system activation (activated stroma). Additionally, in the estrogen receptor-positive subgroup, proteins related to the regulation of insulin-like growth factor transport and platelet degranulation displayed higher abundance, confirming the presence of a proliferative microenvironment. Thus, as conclusions: We debuted a differential bioinformatics workflow for the proteomic analysis of NAF, validating this secretome as a treasure-trove for studying a paired-organ cancer type.
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