1. Integrated copy number and miRNA expression analysis in triple negative breast cancer of Latin American patients
- Author
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Kepher H. Makambi, Rodrigo Coutinho de Almeida, Bruna M. Sugita, Saurabh Kirolikar, Silma Regina Ferreira Pereira, Iglenir J. Cavalli, Rubens Silveira de Lima, Simina M. Boca, Subha Madhavan, Mandeep Gill, Enilze Maria de Souza Fonseca Ribeiro, Yuriy Gusev, Paolo Fadda, Akanksha Mahajan, Cicero Urban, Anju Duttargi, and Luciane R. Cavalli
- Subjects
latinas ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Biology ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Mirna expression ,copy number ,Internal medicine ,microRNA ,Tumor stage ,medicine ,Mirna profiling ,Gene ,Triple-negative breast cancer ,disparities ,3. Good health ,Tumor Subtype ,030104 developmental biology ,030220 oncology & carcinogenesis ,triple-negative breast cancer ,Research Paper - Abstract
Triple negative breast cancer (TNBC), a clinically aggressive breast cancer subtype, affects 15–35% of women from Latin America. Using an approach of direct integration of copy number and global miRNA profiling data, performed simultaneously in the same tumor specimens, we identified a panel of 17 miRNAs specifically associated with TNBC of ancestrally characterized patients from Latin America, Brazil. This panel was differentially expressed between the TNBC and non-TNBC subtypes studied (p ≤ 0.05, FDR ≤ 0.25), with their expression levels concordant with the patterns of copy number alterations (CNAs), present mostly frequent at 8q21.3-q24.3, 3q24-29, 6p25.3-p12.2, 1q21.1-q44, 5q11.1-q22.1, 11p13-p11.2, 13q12.11-q14.3, 17q24.2-q25.3 and Xp22.33-p11.21. The combined 17 miRNAs presented a high power (AUC = 0.953 (0.78–0.99);95% CI) in discriminating between the TNBC and non-TNBC subtypes of the patients studied. In addition, the expression of 14 and 15 of the 17miRNAs was significantly associated with tumor subtype when adjusted for tumor stage and grade, respectively. In conclusion, the panel of miRNAs identified demonstrated the impact of CNAs in miRNA expression levels and identified miRNA target genes potentially affected by both CNAs and miRNA deregulation. These targets, involved in critical signaling pathways and biological functions associated specifically with the TNBC transcriptome of Latina patients, can provide biological insights into the observed differences in the TNBC clinical outcome among racial/ethnic groups, taking into consideration their genetic ancestry.
- Published
- 2019