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AGR2 and AGR3 play an important role in the clinical characterization and prognosis of basal like breast cancer

  • Carolina Leão de Moraes
    Correspondence
    Address for correspondence: Carolina Leão De Moraes, MD, Federal University of Goias: Universidade Federal de Goias,1ª Avenida, s/n - Setor Universitário – Goiânia – Goiás – CEP: 74605-050 – BRAZIL
    Affiliations
    Department of Gynaecology and Obstetrics, Faculty of Medicine, Federal University of Goiás, Goiânia, Brazil
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  • Natália Cruz e Melo
    Affiliations
    Department of Gynaecology and Obstetrics, Faculty of Medicine, Federal University of São Paulo, São Paulo, Brazil
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  • Maira Andrea Valoyes Valoyes
    Affiliations
    Discipline of Oncology, Department of Radiology and Oncology, Faculty of Medicine, University of Sao Paulo, Sao Paulo, Brazil

    Laboratory of Molecular Genetics, Center for Translational Research in Oncology (LIM24), Cancer Institute of Sao Paulo, Sao Paulo, Brazil
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  • Waldemar Naves do Amaral
    Affiliations
    Department of Gynaecology and Obstetrics, Faculty of Medicine, Federal University of Goiás, Goiânia, Brazil

    Graduate Program in Health Sciences, Faculty of Medicine, Federal University of Goiás, Goiânia, Brazil
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      Abstract

      Introduction: Basal-like Breast Cancer (BLBC) represents an important molecular subtype of breast cancer characterized by an aggressive behavior, molecular pathology poorly understood and a limited treatment. Objective: We aim to search for molecular differences between non-BLBC and BLBC tumors in order to propose possible diagnostic and prognostic biomarkers using databases. Metodology: Microarray processed data were downloaded from GEO database considering non-BLBC and BLBC. Enrichment analysis was evaluated using GO consortium and Ingenuity, protein–protein interaction, gene Ontology and co-expression analysis using STRING. Gene expression data was extracted using TCGA, METABRIC and Breast Cancer Gene-Expression Miner v4.2 databases. The Survival was evaluated using The Kaplan–Meier plotter. Results: Were identified 58 upregulated and 58 downregulated genes enriched in signaling pathways like PDGF, Angiogenesis, Integrin and WNT. AGR2 and AGR3 expression were reduced in BLBC in relation to non-BLBC tumors, patients aged ≤51 years, and with negativity of ER, PR and HER-2 and nodal status. Low expression of AGR2 and AGR3 were associated with worse OS and RFS for all breast cancer cases. But according to the molecular stratification, low AGR2 conferred worst OS in luminal A, worst RFS in BLBC and good OS and RFS in luminal B. High AGR3 conferred worse OS and RFS in BLBC, but low AGR3 attributed worse OS in luminal A. Conclusion: AGR2 and AGR3 expression were able to differentiate non-BLBC from BLBC. Downregulation of AGR2 and AGR3 was associated with BLBC clinical phenotype. Furthermore, both genes behave different when considering prognosis and molecular stratification.

      Keywords

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