139. Serum MicroRNA miR-155-5p as a potential biomarker of degenerative disc disease in patients with low back pain

BACKGROUND CONTEXT MicroRNAs (miRNAs) are a class of stable, noncoding RNA molecules that are dysregulated in various disease states and are readily detected in the serum, making them useful biomarkers. Prior studies have found down regulation of local levels of miR-155-5p in degenerative disc tissue, directly increasing Fas-mediated apoptosis of nucleus pulposus cells. However, no studies are currently assessing whether these changes are detectable in the serum. PURPOSE To determine the serum concentration of miR-155-5p in patients with degenerative disc disease (DDD) undergoing lumbar fusion and compare with young, healthy controls. STUDY DESIGN/SETTING Prospective cohort study. PATIENT SAMPLE Sixty-three patients undergoing a single-level lumbar fusion with a Pfirrmann grade of 3, 4 or 5 on MRI T2 sequence were prospectively enrolled at a high-volume academic center. Patients with a history of previous surgery, active infection or systemic chronic illnesses such as diabetes, autoimmune diseases, or malignancy were excluded. Samples from 15 healthy controls were obtained for comparison. OUTCOME MEASURES Fold change of miR-155-5p expression level in patients with DDD compared to healthy controls. Preoperative ODI, SF-12 PCS and MCS, VAS Back and VAS Leg scores. METHODS After informed consent was obtained in the preoperative area, a venous whole blood sample was collected and transported to the laboratory for isolation of serum and storage. miRNA was extracted from the serum using a commercially available kit. Real-time RT-PCR analysis was completed for confirmation of gene expression using TaqMan™ primers for human miR-155-5p. Bioinformatics analysis was completed using Ingenuity Pathway Analysis (Qiagen, Germany). RESULTS Average age for patients in the DDD group was 57.5 ± 13.6 compared to 29.5 ± 10.2 in the control group. In the DDD group, 11.1% of patients were Pfirrmann grade 3, 54.0% were grade 4, 34.9% were grade 5. Average preoperative patient-reported outcomes were: ODI 41.9 ± 18.4, SF-12 PCS 32.2 ± 8.6, SF-12 MCS 46.4 ± 11.3, VAS Back 6.43 ± 2.94, and VAS Leg 6.13 ± 3.05. Serum levels of miR-155-5p were significantly decreased in the DDD group (Fold change −8.523 [-11.585, −5.461]) compared to the healthy control group. Bioinformatics analysis showed involvement of miR-155-5p in mostly cellular development and cellular growth and proliferation pathways. It also showed significant interactions with cell cycle and apoptosis pathways (P38/MAPk, Akt) as well as with pro-inflammatory cytokines. CONCLUSIONS Local levels of miR-155-5p have been shown to be down regulated in DDD by increasing Fas-mediated apoptosis in nucleus pulposus cells. However, this is the first study to detect down regulation of miR-155-5p in the serum of patients with DDD, correlating with local tissue levels and potentially providing a useful biomarker for detecting early degenerative change. Further studies are needed to identify other miRNAs involved in the regulation of intervertebral disc degeneration to create a robust gene profile. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.