Identification of Serum miR-146a and miR-155 as Novel Noninvasive Complementary Biomarkers for Ankylosing Spondylitis

Spine (Phila Pa 1976). 2016 May;41(9):735-42. doi: 10.1097/BRS.0000000000001339.

Abstract

Study design: Prospective serum microRNAs study.

Objective: To investigate differentially expressed serum microRNAs (miRNAs) between ankylosing spondylitis (AS) patients and controls, and to evaluate the potential of miRNAs as biomarkers for AS.

Summary of background data: There is an urgent need to explore novel biomarkers with more high sensitivity and specificity for the diagnosis of AS, especially for early-stage AS. Recently, the discovery of miRNAs has paved a new avenue for the diagnosis of cancers and other diseases, However, the global serum miRNAs pattern in AS patients has never been determined.

Methods: An initial screening of miRNA expression by Solexa sequencing was performed using serum samples pooled from 10 AS patients and 10 controls, respectively. Subsequently, differential expression was validated using hydrolysis probe-based stem-loop quantitative reverse transcription polymerase chain reaction (qRT-PCR). Furthermore, AS patients were divided into group A (kyphosis <70°) and group B (kyphosis ≥70°). Disease activity and functional status were evaluated by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI), respectively. The areas under the receiver-operating characteristic (ROC) curves of identified miRNAs were analyzed.

Results: Nineteen serum miRNAs were differentially expressed in AS patients compared with controls. After qRT-PCR confirmation, miR-146a and miR-155 were significantly upregulated in AS patients. The areas under the ROC curves using miR-146a and miR-155 were 0.917 and 0.964, respectively. Importantly, the miR-155 expression level in group B was significantly higher than that in group A. In addition, significant correlation was observed between miR-155 expression level and BASDAI (r = 0.5, P < 0.01).

Conclusion: Detection of serum miRNAs (miR-146a and miR-155) may serve as novel complementary biomarkers for AS. Moreover, the expression level of miR-155 is suggested to be associated with disease activity and the severity of thoracolumbar kyphosis secondary to AS.

Level of evidence: NA.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Case-Control Studies
  • Female
  • Gene Expression Profiling / methods
  • Humans
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • Middle Aged
  • Prospective Studies
  • Spondylitis, Ankylosing / blood*
  • Spondylitis, Ankylosing / diagnosis*
  • Spondylitis, Ankylosing / genetics
  • Young Adult

Substances

  • Biomarkers
  • MIRN146 microRNA, human
  • MIRN155 microRNA, human
  • MicroRNAs