학술논문
Differential proteomic comparison of breast cancer secretome using a quantitative paired analysis workflow.
Document Type
Academic Journal
Author
Brunoro GVF; Laboratory of Toxinology, Oswaldo Cruz Institute, Fiocruz, Av. Brasil 4365, Manguinhos, Rio de Janeiro, 21040-360, Brazil.; Carvalho PC; Laboratory for Proteomics and Protein Engineering, Carlos Chagas Institute, Fiocruz, Rua Prof. Algacyr Munhoz Mader 3775, CIC, Paraná, 81350-010, Brazil.; Barbosa VC; Systems Engineering and Computer Science Program, Federal University of Rio de Janeiro, Caixa Postal 68511, Ilha do Fundão, Rio de Janeiro, 21941-972, Brazil.; Pagnoncelli D; Laboratory of Applied Molecular Biology, Gynecology Department, Fernandes Figueira Institute, Fiocruz, Av. Rui Barbosa 716, Flamengo, Rio de Janeiro, 22250-020, Brazil.; De Moura Gallo CV; Laboratory of Molecular Biology of Tumors, Department of Genetics, State University of Rio de Janeiro, Rua São Francisco Xavier 524, Maracanã, Rio de Janeiro, 20550-900, Brazil.; Perales J; Laboratory of Toxinology, Oswaldo Cruz Institute, Fiocruz, Av. Brasil 4365, Manguinhos, Rio de Janeiro, 21040-360, Brazil.; Zahedi RP; Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V, Otto-Hahn-Straße 6b, 44227, Dortmund, Germany.; Segal Cancer Proteomics Centre, Lady Davis Institute at the Jewish General Hospital, McGill University, 3755 Chemin de la Côte-Sainte-Catherine, Montréal, H3T 1E2, Canada.; Valente RH; Laboratory of Toxinology, Oswaldo Cruz Institute, Fiocruz, Av. Brasil 4365, Manguinhos, Rio de Janeiro, 21040-360, Brazil.; Neves-Ferreira AGDC; Laboratory of Toxinology, Oswaldo Cruz Institute, Fiocruz, Av. Brasil 4365, Manguinhos, Rio de Janeiro, 21040-360, Brazil. anag@ioc.fiocruz.br.
Source
Publisher: BioMed Central Country of Publication: England NLM ID: 100967800 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2407 (Electronic) Linking ISSN: 14712407 NLM ISO Abbreviation: BMC Cancer
Subject
Language
English
Abstract
Background: 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.
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.
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.
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.
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.
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.
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.