Integrated MicroRNA and mRNA Signatures Associated with Survival in Triple Negative Breast Cancer

• DOI: 10.1371/journal.pone.0055910
• Publication Date: 2013-02-06T22:16:39Z
• Authors: Luciano Cascione; Pierluigi Gasparini; Francesca Lovat; Stefania Carasi; Alfredo Pulvirenti; Alfredo Ferro; Hansjuerg Alder; Gang He; Andrea Vecchione; Carlo M. Croce; Charles L. Shapiro; Kay Huebner
• Keywords: Triple-negative breast cancer

Triple negative breast cancer (TNBC) is a heterogeneous disease at the molecular, pathologic and clinical levels. To stratify TNBCs, we determined microRNA (miRNA) expression profiles, as well profiles of cancer-focused mRNA panel, in tumor, adjacent non-tumor (normal) lymph node metastatic lesion (mets) tissues, from 173 women with TNBCs; linked specific miRNA signatures to patient survival used miRNA/mRNA anti-correlations identify clinically genetically different TNBC subclasses. We also assessed potential regulators subclass-specific gene networks defined by canonical signal pathways. Tissue miRNAs mRNAs were identified for normal vs tumor mets comparisons. correlated prognosis predicted anti-correlated targets within profile defined. Two (miR-16, 155, 125b, 374a miR-16, 374a, 374b, 421, 655, 497) predictive overall (P = 0.05) distant-disease free 0.009), respectively, patients 50 yrs age or younger. By multivariate analysis risk independent predictors survival. profiling, using resulted clustering TNBCs into 4 molecular subclasses prognostic miRNAs. Our findings suggest that play key role triple through their ability regulate fundamental pathways such as: cellular growth proliferation, movement migration, Extra Cellular Matrix degradation. The results define characterize contribute phenotypic diversity its metastasis.