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.