Prognostic role of elevated mir-24-3p in breast cancer and its association with the metastatic process

// Alireza Khodadadi-Jamayran 1 , Betul Akgol-Oksuz 2 , Yelena Afanasyeva 3 , Adriana Heguy 4, 5 , Marae Thompson 6 , Karina Ray 5 , Ariadna Giro-Perafita 6 , Irma Sanchez 4 , Xifeng Wu 7 , Debu Tripathy 8 , Anne Zeleniuch-Jacquotte 3 , Aristotelis Tsirigos 1, 4 and Francisco J. Esteva 6 1 Applied Bioinformatics Laboratories, NYU School of Medicine, New York, NY, USA 2 Department Bioinformatics and Computational Biology, University of Massachusetts Medical School, Worcester, MA, USA 3 Division of Epidemiology, NYU School of Medicine, New York, NY, USA 4 Department of Pathology, NYU School of Medicine, New York, NY, USA 5 Genome Technology Center, NYU School of Medicine, New York, NY, USA 6 Division of Hematology/Oncology, Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA 7 Department of Epidemiology, UT MD Anderson Cancer Center, Houston, TX, USA 8 Department of Breast Medical Oncology, UT MD Anderson Cancer Center, Houston, TX, USA Correspondence to: Francisco J. Esteva, email: francisco.esteva@nyumc.org Aristotelis Tsirigos, email: Aristotelis.Tsirigos@nyumc.org Keywords: breast cancer; gene expression profiling Received: July 08, 2017     Accepted: January 13, 2018     Published: February 05, 2018 ABSTRACT MicroRNAs have been shown to play important roles in breast cancer progression and can serve as biomarkers. To assess the prognostic role of a panel of miRNAs in breast cancer, we collected plasma prospectively at the time of initial diagnosis from 1,780 patients with stage I-III breast cancer prior to definitive treatment. We identified plasma from 115 patients who subsequently developed distant metastases and 115 patients without metastatic disease. Both groups were matched by: age at blood collection, year of blood collection, breast cancer subtype, and stage. The median follow up was 3.4 years (range, 1-9 years). We extracted RNA from plasma and analyzed the expression of 800 miRNAs using Nanostring technology. We then assessed the expression of miRNAs in primary and metastatic breast cancer samples from The Cancer Genome Atlas (TCGA). We found that, miR-24-3p was upregulated in patients with metastases, both in plasma and in breast cancer tissues. Patients whose primary tumors expressed high levels of miR-24-3p had a significantly lower survival rate compared to patients with low mir-24-3p levels in the TCGA cohort (n=1,024). RNA-Seq data of the samples with the highest miR-24-3p expression versus those with the lowest miR-24-3p in the TCGA cohort identified a specific gene expression signature for those tumors with high miR-24-3p. Possible target genes for miR-24-3p were predicted based on gene expression and binding site, and their effects on cancer pathways were evaluated. Cancer, breast cancer and proteoglycans were the top three pathways affected by miR-24-3p overexpression.