miR-30e is an independent subtype-specific prognostic marker in breast cancer

• Published in: British journal of cancer 2015-07, Vol.113 (2), p.290-298
• Main Authors: D'Aiuto, F, Callari, M, Dugo, M, Merlino, G, Musella, V, Miodini, P, Paolini, B, Cappelletti, V, Daidone, M G
• Format: Article
• Language: English
• Subjects: 631/337/384/331; 692/699/67/1347; 692/699/67/1857; 692/700/1750; Biomedical and Life Sciences; Biomedicine; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cancer Research; Cell Line, Tumor; Drug Resistance; Epidemiology; Estrogen Receptor alpha - analysis; Female; Humans; Lymphatic Metastasis; MicroRNAs - analysis; MicroRNAs - physiology; Molecular Diagnostics; Molecular Medicine; Oncology; Prognosis; Proportional Hazards Models; Receptor, ErbB-2 - analysis; Transcriptome
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2015.206

Background: Breast cancer clinical outcome is affected by tumor molecular features, and the identification of subtype-specific prognostic biomarkers is relevant for breast cancer translational research. Gene expression signatures proved to be able to complement prognostic information provided by classical clinico-pathological features. Recently, microRNAs (miRNAs) have been causally linked to tumorigenesis and cancer progression and have been associated with patient outcome, also in breast cancer. Methods: MicroRNAs associated with the development of distant metastasis were identified in a cohort of 92 ESR1+/ERBB2− lymph node-negative breast cancers from patients not receiving adjuvant treatment. Results were confirmed and further investigated in a total of 1246 miRNA and gene expression profiles of the Molecular Taxonomy of Breast Cancer International Consortium data set. Moderated t -test, univariable and multivariable Cox regression models were used for statistical analyses. Results: miR-30e* was identified as independent protective prognostic factor in lymph node-negative untreated patients with ESR1+/ERBB2− tumours and retained a significant association with a good prognosis in treated patients with the same tumor subtype as well as in the ERBB2+ subtype, but not in ESR1−/ERBB2− tumours. Conclusions: We highlighted a relevant and subtype-specific role in breast cancer for miR-30e* and demonstrated that adding miRNA markers to gene signatures and clinico-pathological features can help for a better prognostication.