MicroRNA-155 expression is independently predictive of outcome in chordoma.

Eiji Osaka,Zhenfeng Duan,Jacson K Shen,Henry J Mankin,Dimitrios Spentzos,Francis J Hornicek,Edwin Choy,Xiaoqian Yang,Pei Yang,Andrew D Kelly

doi:10.18632/oncotarget.3273

Abstract

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. 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. 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. 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.

Highlights

Chordoma is a rare, low-grade bone cancer arising from benign notochordal rests [1]
To identify those miRs most likely to be biologically active in chordoma, we performed an independent analysis of miR regulatory activity which utilizes mRNA expression data in conjunction with miR target transcript prediction algorithms to infer the relative biological action of specific miRs
Because miR-155 was found to have higher expression in chordoma tissue relative to normal ( p = 0.018; Supplementary Table S1, S2), and its role has been characterized in other malignancies, we chose to further investigate its biological relevance in chordoma

Summary

Introduction

Low-grade bone cancer arising from benign notochordal rests [1]. Chordoma develops asymptomatically with local invasion and slow growth. The optimal treatment for chordoma is wide surgical resection, which has been shown to decrease local recurrence and metastasis [3,4,5]. It is frequently difficult to adequately achieve negative surgical margins because of tumor www.impactjournals.com/oncotarget location and adjacent critical vital structures. More than 40% of patients with chordoma experience local recurrence. Chordomas can metastasize several years after the initial diagnosis, with 10–50% of patients developing metastases during follow-up. There is an unmet need to explore new prognostic markers and therapeutic approaches for chordoma patients. 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

Objectives

Methods

Results

Conclusion