Abstract A25: Differences in microRNA expression patterns in breast cancer subtypes

Abstract

Abstract Breast cancer can be classified according to the gene expression signatures of the tumors into four clinically relevant sub-types, luminal A, luminal B, Her2-like and basal-like. Additionally microRNA expression patterns can separate normal tissue from breast tumors, but there is currently limited information about the potential differences in microRNA expression profiles between the different tumor subtypes, defined by gene expression. In order to determine the microRNA expression profiles in breast tumors, and explore the differences in the expression patterns of these molecules between different cancer subtypes, we analyzed the expression of 664 microRNAs with the TaqMan low-density array platform in 40 breast tumors from different subtypes, and in 21 adjacent normal breast tissues. Tumor sub-typing was carried out with the PAM50 algorithm in expression data obtained with the Affymetrix Human Gene ST 1.0 array, obtaining 8 Luminal A tumors, 9 luminal B, 8 Her2-like and 3 Triple negative basal-like tumors. Given the low number of basal-like tumors, for the microRNA expression analysis, we included 12 additional triple-negative tumors defined by immunohistochemistry. Finally, we analyzed the expression of DICER and Ago2, involved in the biogenesis of microRNAs in the breast tumors. 131 microRNAs showed significant differential expression (adjusted P value=0.05, Fold Change=2) in breast tumors compared to the normal adjacent tissue. The role of 25% of these microRNAs has not been previously reported in breast cancer. 10 microRNAs showed differential expression between basal/triple negative tumors compared to hormone receptor and HER2 positive tumors. Transcriptional targets of these microRNAs include genes involved in the carcinogenesis of triple negative tumors, like PARP1, or in the microRNA biogenesis machinery, like DICER. Enrichment ontology analysis of the microRNAs differentially expressed in the TN tumors, detected pathways like p53 and focal adhesion whose role in cancer development, invasion and metastasis might be crucial; and MAPK, which has been related to recurrence of TN tumors. Regarding the expression of Ago2 and DICER, we detected down-regulation (approximately 20% less) of both proteins, mainly in TN tumors. Down-regulation in the triple negative tumors was further validated at the mRNA level by RT-qPCR assays. Our data identified the altered expression of several microRNAs whose aberrant expression might have an important impact on cancer-related cellular pathways and whose role in breast cancer has not been previously described. microRNAs expression is also capable to discriminate between different tumor subtypes and the expression of proteins involved in microRNA biogenesis might play a role in breast carcinogenesis, specifically in the triple negative subtype. Citation Format: Sandra L. Romero-Cordoba, Rosa G. Rebollar-Vega, Valeria Quintanar-Jurado, Veronica Bautista-Pina, Sergio Rodriguez-Cuevas, Antonio Maffuz-Aziz, Alfredo Hidalgo-Miranda. Differences in microRNA expression patterns in breast cancer subtypes [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr A25.