Differentially expressed miRNAs in triple negative breast cancer between African-American and non-Hispanic white women
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Bruna Sugita1, Mandeep Gill2, Akanskha Mahajan2, Anju Duttargi2, Saurabh Kirolikar2, Rodrigo Almeida1, Kenny Regis2, Olusayo L. Oluwasanmi2, Fabio Marchi3, Catalin Marian4,8, Kepher Makambi2,5, Bhaskar Kallakury6, Laura Sheahan7, Iglenir J.Cavalli1, Enilze M. Ribeiro1, Subha Madhavan2,7, Simina Boca2,7, Yuriy Gusev2,7, Luciane R. Cavalli2
1Department of Genetics, Federal University of Paraná, Curitiba, PR, Brazil
2Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA
3International Research Center-CIPE, A. C. Camargo Cancer Center, São Paulo, SP, Brazil
4The Ohio State University Comprehensive Cancer Center, Division of Cancer Prevention and Control, College of Medicine, The Ohio State University, Columbus, Ohio
5Departments of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University, Washington, DC USA
6Department of Pathology, Georgetown University Medical Center, Washington, DC, USA
7Innovation Center for Biomedical Informatics, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA
8The University of Medicine and Pharmacy Timisoara, Timisoara, Romania
Luciane R. Cavalli, email: firstname.lastname@example.org
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
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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