MicroRNA-155 expression is independently predictive of outcome in chordoma

Abstract

// Eiji Osaka 1, 2 , Andrew D. Kelly 3 , Dimitrios Spentzos 4 , Edwin Choy 1 , Xiaoqian Yang 1 , Jacson K. Shen 1 , Pei Yang 1 , Henry J. Mankin 1 , Francis J. Hornicek 1 , Zhenfeng Duan 1 1 Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA 02114, USA 2 Department of Orthopaedic Surgery, Nihon University School of Medicine, Tokyo 173–8610, Japan 3 Fels Institute for Cancer Research & Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA 4 Division of Hematology/Oncology, Sarcoma Program, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA Correspondence to: Zhenfeng Duan, e-mail: zduan@mgh.harvard.edu Keywords: miRNA-155 (miR-155), chordoma, prognosis, miRNA microarray assay, RT-PCR Received: November 19, 2014      Accepted: February 07, 2015      Published: March 16, 2015 ABSTRACT Background: Chordoma pathogenesis remains poorly understood. In this study, we aimed to evaluate the relationships between microRNA-155 (miR-155) expression and the clinicopathological features of chordoma patients, and to evaluate the functional role of miR-155 in chordoma. Methods: The miRNA expression profiles were analyzed using miRNA microarray assays. Regulatory activity of miR-155 was assessed using bioinformatic tools. miR-155 expression levels were validated by reverse transcription-polymerase chain reaction. The relationships between miR-155 expression and the clinicopathological features of chordoma patients were analyzed. Proliferative, migratory and invasive activities were assessed by MTT, wound healing, and Matrigel invasion assays, respectively. Results: The miRNA microarray assay revealed miR-155 to be highly expressed and biologically active in chordoma. miR-155 expression in chordoma tissues was significantly elevated, and this expression correlated significantly with disease stage ( p = 0.036) and the presence of metastasis ( p = 0.035). miR-155 expression also correlated significantly with poor outcomes for chordoma patients (hazard ratio, 5.32; p = 0.045). Inhibition of miR-155 expression suppressed proliferation, and the migratory and invasive activities of chordoma cells. Conclusions: We have shown miR-155 expression to independently affect prognosis in chordoma. These results collectively indicate that miR-155 expression may serve not only as a prognostic marker, but also as a potential therapeutic target in chordoma.