Differentially expressed miRNAs in triple negative breast cancer between African-American and non-Hispanic white women.
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.
Department of Genetics, Federal University of Paraná, Curitiba, PR, Brazil.
Bruna
B
Sugita
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
Mandeep
M
Gill
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
Akanskha
A
Mahajan
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
Anju
A
Duttargi
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
Saurabh
S
Kirolikar
Department of Genetics, Federal University of Paraná, Curitiba, PR, Brazil.
Rodrigo
R
Almeida
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
Kenny
K
Regis
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
Olusayo L
OL
Oluwasanmi
International Research Center-CIPE, A. C. Camargo Cancer Center, São Paulo, SP, Brazil.
Fabio
F
Marchi
The Ohio State University Comprehensive Cancer Center, Division of Cancer Prevention and Control, College of Medicine, The Ohio State University, Columbus, Ohio.|The University of Medicine and Pharmacy Timisoara, Timisoara, Romania.
Catalin
C
Marian
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.|Departments of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University, Washington, DC USA.
Kepher
K
Makambi
Department of Pathology, Georgetown University Medical Center, Washington, DC, USA.
Bhaskar
B
Kallakury
Innovation Center for Biomedical Informatics, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
Laura
L
Sheahan
Department of Genetics, Federal University of Paraná, Curitiba, PR, Brazil.
Iglenir J
IJ
Cavalli
Department of Genetics, Federal University of Paraná, Curitiba, PR, Brazil.
Enilze M
EM
Ribeiro
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.|Innovation Center for Biomedical Informatics, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
Subha
S
Madhavan
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.|Innovation Center for Biomedical Informatics, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
Simina
S
Boca
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.|Innovation Center for Biomedical Informatics, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
Yuriy
Y
Gusev
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
Luciane R
LR
Cavalli
D001741:Black or African American / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D012372:ROC Curve; D015398:Signal Transduction; D064726:Triple Negative Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D044465:White People / Q000235:genetics*
African American; copy number; microRNA; non-Hispanic white; triple negative breast cancer