Abstract P4-07-04: A distinctive miRNA profile highlights breast cancer in very young women (BCVY) as a new molecular subgroup

Abstract

Abstract Background: Although less frequent (1% of all breast cancer) than in older women, breast cancer (BC) in very young women (BCVY),(≤35 years old) often exhibits larger tumor sizes, high pathological grade, high proliferation percentage, nodal involvement, and greater HER2+ percentage, usually associated with a poorer prognosis. BC and BCVY might arise as different disease entities derived from different underlying mechanisms. MicroRNAs (miRNAs) are short RNA molecules with post-transcriptional regulatory function, usually silencing targeted mRNAs. Recently, miRNA profiling has arisen as major approaching study technique, demonstrating a widespread miRNA deregulation in various tumor types. In this study we offer a miRNA profile of a subset of BCVY patients and evaluate whether there are any miRNA deregulated pointing out some pathway to better understand the ongoing mechanism and characterize BCVY as a new molecular entity. Material and methods: We performed a comprehensive study of miRNA expression using miRNA Affymetrix 2.0 array. We extracted RNA from FFPE tumor tissue of both 44 BC patients ≤35years (BCVY) and 46 older than 45years in two age groups (45-65 and >65), we used normal breast tissue as control and evaluated the differences in expression of each age group. We tried to validate most interesting miRNA by qRT-PCR. We performed enrichment analysis of multiple miRNA target genes (DIANA mirpath) to search for putative pathways that could be deregulated by the miRNAs. Results: We obtained a differential and unique miRNA expression profile of 121 miRNAs (p-value<0.05), 96 of those with FDR<0.05. After hierarchical clustering, samples were unsupervised grouped according to their age, neither by subtype nor by tumor characteristics. Of the 11 miRNA selected for validation, we were able to validate differences in the expression of 6 miRNAs: miR-1228*, miR-3196, miR-1275, miR-92b, miR-139, miR-1207, moreover, all of the miRNAs maintained the expression's trend. The validated miRNAs pointed out pathways related with cell motility and invasion (adherens junction, chondroitin sulfate biosynthesis, cell adhesion molecules) and cell proliferation (calcium signaling, wnt signaling). Conclusion: We performed a comprehensive study of the miRNA expression on a total of 89 BC patients, detecting a differential molecular profile in BCVY patients, suggesting that there might be a different underlying mechanism and that BCVY could be identified as a different entity. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-07-04.