Produção Nacional
Differentially expressed miRNAs in triple negative breast cancer between African-American and non-Hispanic white women
2016; Impact Journals LLC; Volume: 7; Issue: 48 Linguagem: Inglês
10.18632/oncotarget.13024
ISSN1949-2553
AutoresBruna M. Sugita, Mandeep Gill, Akanskha Mahajan, Anju Duttargi, Saurabh Kirolikar, Rodrigo Coutinho de Almeida, Kenny Regis, Olusayo L. Oluwasanmi, Fábio Albuquerque Marchi, Cătălin Marian, Kepher H. Makambi, Bhaskar Kallakury, Laura Sheahan, Iglenir João Cavalli, Enilze Maria de Souza Fonseca Ribeiro, Subha Madhavan, Simina M. Boca, Yuriy Gusev, Luciane R. Cavalli,
Tópico(s)Circular RNAs in diseases
Resumo// Bruna Sugita 1 , Mandeep Gill 2 , Akanskha Mahajan 2 , Anju Duttargi 2 , Saurabh Kirolikar 2 , Rodrigo Almeida 1 , Kenny Regis 2 , Olusayo L. Oluwasanmi 2 , Fabio Marchi 3 , Catalin Marian 4, 8 , Kepher Makambi 2, 5 , Bhaskar Kallakury 6 , Laura Sheahan 7 , Iglenir J. Cavalli 1 , Enilze M. Ribeiro 1 , Subha Madhavan 2, 7 , Simina Boca 2, 7 , Yuriy Gusev 2, 7 , Luciane R. Cavalli 2 1 Department of Genetics, Federal University of Paraná, Curitiba, PR, Brazil 2 Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA 3 International Research Center-CIPE, A. C. Camargo Cancer Center, São Paulo, SP, Brazil 4 The Ohio State University Comprehensive Cancer Center, Division of Cancer Prevention and Control, College of Medicine, The Ohio State University, Columbus, Ohio 5 Departments of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University, Washington, DC USA 6 Department of Pathology, Georgetown University Medical Center, Washington, DC, USA 7 Innovation Center for Biomedical Informatics, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA 8 The University of Medicine and Pharmacy Timisoara, Timisoara, Romania Correspondence to: Luciane R. Cavalli, email: lrc@georgetown.edu Keywords: microRNA, triple negative breast cancer, African American, non-Hispanic white, copy number Received: July 02, 2016 Accepted: October 25, 2016 Published: November 02, 2016 ABSTRACT Triple Negative Breast Cancer (TNBC), a clinically aggressive subtype of breast cancer, disproportionately affects African American (AA) women when compared to non-Hispanic Whites (NHW). MiRNAs(miRNAs) play a critical role in these tumors, through the regulation of cancer driver genes. In this study, our goal was to characterize and compare the patterns of miRNA expression in TNBC of AA ( n = 27) and NHW women ( n = 30). A total of 256 miRNAs were differentially expressed between these groups, and distinct from the ones observed in their respective non-TNBC subtypes. Fifty-five of these miRNAs were mapped in cytobands carrying copy number alterations (CNAs); 26 of them presented expression levels concordant with the observed CNAs. Receiving operating characteristic (ROC) analysis showed a good power (AUC ≥ 0.80; 95% CI) for over 65% of the individual miRNAs and a high combined power with superior sensitivity and specificity (AUC = 0.88 (0.78−0.99); 95% CI) of the 26 miRNA panel in discriminating TNBC between these populations. Subsequent miRNA target analysis revealed their involvement in the interconnected PI3K/AKT, MAPK and insulin signaling pathways. Additionally, three miRNAs of this panel were associated with early age at diagnosis. Altogether, these findings indicated that there are different patterns of miRNA expression between TNBC of AA and NHW women and that their mapping in genomic regions with high levels of CNAs is not merely physical, but biologically relevant to the TNBC phenotype. Once validated in distinct cohorts of AA women, this panel can potentially represent their intrinsic TNBC genome signature.
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