Abstract
Purpose
Aberrant expression of miRNAs has been demonstrated to contribute to human carcinogenesis. This study was aimed at profiling differentially expressed miRNAs in formalin-fixed and paraffin-embedded tissues of spinal chordoma and testing the potential for using altered expression of miRNAs as prognostic markers for spinal chordoma patients.
Methods
A miRNA array was used to profile differentially expressed miRNAs in spinal chordoma and nucleus pulposus tissues. Four of these differentially expressed miRNAs was then validated in spinal chordoma and control patients using quantitative RT-PCR. Bioinformatical analysis identified potential GO terms and signaling pathways affected by these microRNAs. Altered miR-1237-3p expression was then found to be associated with clinicopathological characteristics and prognosis of spinal chordoma patients.
Results
The miRNA arrays identified 29 differentially expressed miRNAs in spinal chordoma tissues, four of which were verified by qRT-PCR in 42 spinal chordomas and 14 control tissues. Bioinformatical analysis revealed that the potential target genes of these miRNAs were mainly involved in gene transcription, cell junction proteins, and gene pathways in cancer and endocytosis. Reduced miR-1237-3p expression was associated with tumor invasion and worse recurrence-free survival of spinal chordoma patients (χ 2 = 16.217, p = 0.000, log-rank test). Multivariate analyses showed that miR-1237-3p expression was an independent prognostic factor for patients with spinal chordoma (HR = 0.001, 95 % CI 0.000–0.136, p = 0.005).
Conclusion
The data from the current study identified a total of 29 differentially expressed miRNAs in chordoma tissues and reduced miR-1237-3p expression was associated with chordoma invasion and worse recurrence-free survival of the patients.
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Acknowledgments
We would like to thank OE Bio-tech (Shanghai, China) for technical support of this study. We also thank Medjaden Bioscience Limited (Hong Kong, China) for assistance in preparation of this manuscript.
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The authors declare that there is no conflict of interest in this work.
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586_2015_3927_MOESM2_ESM.jpg
Supplementary material 2. Analysis of miRNA–gene GO network. The blue box represents down-regulated miRNA-repressed gene (mRNA), red square represents down-regulated miRNA, and green square represents significant GO terms regulated by these miRNAs. The relationship between miRNAs, target genes and GOs are represented by gray lines. (JPEG 1333 kb)
586_2015_3927_MOESM3_ESM.jpg
Supplementary material 3. Analysis of miRNA–gene network. The blue box represents up-regulated miRNA-repressed genes (mRNA) and the red square represents up-regulated miRNA. The relationship between miRNAs and the target genes are represented by gray lines. (JPEG 3051 kb)
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Zou, Mx., Huang, W., Wang, Xb. et al. Reduced expression of miRNA-1237-3p associated with poor survival of spinal chordoma patients. Eur Spine J 24, 1738–1746 (2015). https://doi.org/10.1007/s00586-015-3927-9
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DOI: https://doi.org/10.1007/s00586-015-3927-9