MicroRNA-10a, -210, and -563 as circulating biomarkers for ossification of the posterior longitudinal ligament

Abstract

Background context: The presence of ossification of posterior longitudinal ligament (OPLL) can lead to symptomatic spinal cord compression and myelopathy. The surgical approach in patients with myelopathy is influenced by the presence of OPLL. Diagnose of OPLL currently requires computed tomography which incurs a large dose of radiation. Circulating disease-specific microRNAs (miRNAs) may serve as promising diagnostic markers with no radiation and easy accessibility for OPLL patients.

Purpose: The purpose of this study is to evaluate the accuracy and significance of OPLL-specific microRNAs in discriminating OPLL from normal and intervertebral disc degenerated (IDD) patients by detecting the microRNAs' plasma level.

Study design/patient samples: The level of microRNAs in OPLL patients' plasma or serum were detected and compared to that of normal and IDD patients to evaluate the accuracy and significance of diagnosing OPLL.

Methods: Taking advantage of the high through-put microRNA sequencing data, we selectively tested the ten most differentially regulated microRNAs in patients with: (1) radiologically diagnosed OPLL (n = 68), (2) radiologically diagnosed disc herniated patients with no evidence of OPLL (n = 45), (3) non-OPLL and nonmyelopathy patients (n = 53).The feasibility of the biomarkers in identifying OPLL was assessed through analysis of sensitivity, specificity, accuracy, negative predictive value, positive predictive value, and area under the curve (AUC) values.

Results: Of the ten miRNAs validated, miR-10a-3p, miR-10a-5p, miR-563, miR-210-3p, and miR-218-3p showed significance between OPLL and non-OPLL blood samples. While miR-10a-5p, miR-563, and miR-210-3p showed high accuracy and significance in identifying OPLL from other groups individually, and an index that combines these miRNAs achieved the highest accuracy and AUC among these individual miRNAs.

Conclusions: Analysis of miR-10a-5p, miR-563, and miR-210-3p may be of important value in diagnosing OPLL. These markers maybe useful in a clinical setting in the early detection of OPLL patients by blood testing.

Keywords: Diagnostic markers; MicroRNAs; OPLL; Serum marker.