Circulating microRNAs May Be Predictive of Degenerative Cervical Myelopathy

Srikanth N Divi; Dessislava Z Markova; Nicholas D D'Antonio; Mark J Lambrechts; Hannah A Levy; Jeremy C Heard; Goutham R Yalla; Michael Chang; Alan S Hilibrand; Alexander R Vaccaro; Christopher K Kepler

doi:10.1097/BRS.0000000000005025

Circulating microRNAs May Be Predictive of Degenerative Cervical Myelopathy

Spine (Phila Pa 1976). 2024 May 6. doi: 10.1097/BRS.0000000000005025. Online ahead of print.

Authors

Srikanth N Divi¹, Dessislava Z Markova², Nicholas D D'Antonio², Mark J Lambrechts^{2

3}, Hannah A Levy², Jeremy C Heard², Goutham R Yalla², Michael Chang^{2

3}, Alan S Hilibrand^{2

3}, Alexander R Vaccaro^{2

3}, Christopher K Kepler^{2

3}

Affiliations

¹ Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60614.
² Department of Orthopaedic Surgery, Sidney Kimmel School of Medicine, Thomas Jefferson University, Philadelphia, PA.
³ Rothman Institute, Philadelphia, PA.

PMID: 38711175
DOI: 10.1097/BRS.0000000000005025

Abstract

Study design: Basic Science.

Objective: The objective of this study was to identify a unique serum profile of circulating miRNAs and inflammatory markers in patients with degenerative cervical myelopathy (DCM) compared to healthy controls (HC).

Summary of background data: Currently, DCM is diagnosed with a combination of history, physical examination, and close correlation to advanced imaging. To date, no serum marker has been identified to be diagnostic of this condition.

Methods: Whole venous blood was collected from patients with DCM as well as healthy age- and sex-matched controls. miRNA was extracted from venous blood and a screening analysis was initially conducted to identify miRNA dysregulation in DCM patients. RT-qPCR was used to analyze the expression of 2 specific miRNAs based on screening analysis and literature review. Bioinformatics analysis was used to identify gene networks and potential targets of the miRNA. In addition, the serum inflammatory profile of DCM and HC groups was differentiated using a pro-inflammatory panel.

Results: Thirty-six patients were enrolled in the DCM group (36.1% male, 61.5±9.5 y) while 35 patients were enrolled in the HC group (31.4% male, 57.5±8.9 y). Of the 15 total miRNAs differentially expressed between DCM and HC groups, two were selected for further analysis: miR-223-3p (upregulated) and miR-451a (downregulated). Functional gene network analysis revealed the highest-ranking gene network was involved in neurological disease, while the most overexpressed miRNA in this network (miR-233-3p) was noted to have over 100 targets including CDKN1B and the insulin receptor. Serum cytokine analysis showed significant upregulation of several pro-inflammatory cytokines in the DCM cohort compared to the HC group.

Conclusion: DCM patients demonstrated a set of unique circulating miRNAs in addition to a different serum inflammatory profile compared to HC. These miRNAs may potentially serve as targets for future therapeutic intervention or diagnostic/prognostic testing.