Association of Presurgical Circulating MicroRNAs with 1-Year Postsurgical Pain Reduction in Lumbar Spinal Stenosis Patients with Spine Facet Osteoarthritis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA666660 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12748314.fastq.gz | Fastqsanger.gz | |||
| SRR12748315.fastq.gz | Fastqsanger.gz | |||
| SRR12748316.fastq.gz | Fastqsanger.gz | |||
| SRR12748317.fastq.gz | Fastqsanger.gz | |||
| SRR12748318.fastq.gz | Fastqsanger.gz |
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Project description:OBJECTIVE: Our objective was to sequence the plasma miRNome from 56 patients with lumbar spinal stenosis (LSS) to determine whether miRNA signatures at time of surgery predicted pain responses one year later. MicroRNA libraries were prepared using the QIAseq miRNA Library Kit and sequenced on the Illumina NextSeq550. Counts were produced for microRNAs captured in miRBase
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Project description:PurposeUp to 30% of spine facet osteoarthritis patients with lumbar spinal stenosis (SF-OA + LSS) have little to no improvement in their pain after surgery. Lack of meaningful improvement in pain following surgery provides a unique opportunity to identify specific predictive biomarker signatures that might be associated with the outcomes of surgical treatment. The objective of the present study was to determine whether a microRNA (miRNA) biomarker signature could be identified in presurgical blood plasma that corresponded with levels of SF-OA + LSS patient post-surgical pain intensity one year later.MethodsRNA was extracted from baseline plasma of SF-OA + LSS patients and prepared for miRNA sequencing. Statistical approaches were performed to identify differentially expressed miRNAs associated with reduced 1-year postsurgical pain (n = 56). Using an integrated computational approach, we further created predicted gene and pathway networks for each identified miRNA.ResultsWe identified a panel of 4 circulating candidate miRNAs (hsa-miR-155-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-99b-5p) with higher levels at presurgical baseline that were associated with greater changes in % NPRS20Δ, reflecting reduced pain intensity levels at one year. Genes encoding hsa-let-7e-5p, hsa-miR-125a-5p, and hsa-miR-99b-5p are part of an evolutionarily conserved miRNA cluster. Using integrated computational analyses, we showed that mammalian target of rapamycin, transforming growth factor-β1 receptor, Wnt signaling, epithelial-mesenchymal transition regulators, and cholecystokinin signaling were enriched pathways of predicted gene targets.ConclusionsTaken together, our findings suggest that 4 presurgical baseline circulating miRNAs correlate with 1-year postsurgical SF-OA + LSS patient pain intensity and represent possible candidate biomarker signature of surgical pain response.
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Project description:Given the leading cause of disability worldwide, low back pain (LBP) is recognized as a pivotal socio-economic challenge to the aging population, which is importantly attributed to intervertebral disc degeneration (IVDD), a highly prevalent affliction of aging. Elastic nucleus pulposus (NP) tissue is essential for maintenance of IVD structural and functional integrity. Native NP cells exhibit crucial functions for regulating extracellular matrix homeostasis, constructing an accommodating biomechanical environment and maintaining the gelatinous property of NP tissue. Mechanical stresses, including compulsion position and aberrant mechanical loading, are regarded as etiological factors of IVDD, and to further investigate the effect of mechanical exercise during the degeneration of IVDs, we surgically resected the lumbar 4th-lumbar 5th (L4-L5) spinous processes of the rat spine along with the supraspinous and interspinous ligaments to induce lumbar surgical instability (LSI). Additionally, we applied RNA sequencing technology to describe the degeneration-associated molecular atlas of the LSI model during exercise, and found that exercise accelerated the degenerative process of IVDs from LSI, which is involved in cytosolic DNA sensing-mediated inflammatory activation, similar to the degenerative patterns of the clinical IVDD process.
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Project description:BackgroundLumbar spinal stenosis (LSS) is a common reason for spine surgery in which ligamentum flavum is resected. Transthyretin (TTR) amyloid is an often unrecognized and potentially modifiable mechanism for LSS that can also cause TTR cardiac amyloidosis. Accordingly, older adult patients undergoing lumbar spine (LS) surgery were evaluated for amyloid and if present, the precursor protein, as well as comprehensive characterization of the clinical phenotype.MethodsA prospective, cohort study in 2 academic medical centers enrolled 47 subjects (age 69 ± 7 years, 53% male) undergoing clinically indicated LS decompression. The presence of amyloid was evaluated by Congo Red staining and in those with amyloid, precursor protein was determined by laser capture microdissection coupled to mass spectrometry (LCM-MS). The phenotype was assessed by disease-specific questionnaires (Swiss Spinal Stenosis Questionnaire and Kansas City Cardiomyopathy Questionnaire) and the 36-question short-form health survey, as well as biochemical measures (TTR, retinol-binding protein, and TTR stability). Cardiac testing included technetium-99m-pyrophosphate scintigraphy, electrocardiograms, echocardiograms, and cardiac biomarkers as well as measures of functional capacity.ResultsAmyloid was detected in 16 samples (34% of participants) and was more common in those aged ≥ 75 years of age (66.7%) compared with those <75 years (22.3%, p < 0.05). LCM-MS demonstrated TTR as the precursor protein in 62.5% of participants with amyloid while 37.5% had an indeterminant type of amyloid. Demographic, clinical, quality-of-life measures, electrocardiographic, echocardiographic, and biochemical measures did not differ between those with and without amyloid. Among those with TTR amyloid (n = 10), one subject had cardiac involvement by scintigraphy.ConclusionsAmyloid is detected in more than a third of older adults undergoing LSS. Amyloid is more common with advancing age and is particularly common in those >75 years old. No demographic, clinical, biochemical, or cardiac parameter distinguished those with and without amyloid. In more than half of subjects with LS amyloid, the precursor protein was TTR indicating the importance of pathological assessment.
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Project description:Study designRandomized trial and concurrent observational cohort study.ObjectiveTo compare 4 year outcomes of surgery to nonoperative care for spinal stenosis.Summary of background dataSurgery for spinal stenosis has been shown to be more effective compared to nonoperative treatment over 2 years, but longer-term data have not been analyzed.MethodsSurgical candidates from 13 centers in 11 US states with at least 12 weeks of symptoms and confirmatory imaging were enrolled in a randomized cohort (RC) or observational cohort (OC). Treatment was standard decompressive laminectomy or standard nonoperative care. Primary outcomes were SF-36 bodily pain (BP) and physical function scales and the modified Oswestry Disability index assessed at 6 weeks, 3 months, 6 months, and yearly up to 4 years.ResultsA total of 289 patients enrolled in the RC and 365 patients enrolled in the OC. An as-treated analysis combining the RC and OC and adjusting for potential confounders found that the clinically significant advantages for surgery previously reported were maintained through 4 years, with treatment effects (defined as mean change in surgery group minus mean change in nonoperative group) for bodily pain 12.6 (95% confidence interval [CI], 8.5-16.7); physical function 8.6 (95% CI, 4.6-12.6); and Oswestry Disability index -9.4 (95% CI, -12.6 to -6.2). Early advantages for surgical treatment for secondary measures such as bothersomeness, satisfaction with symptoms, and self-rated progress were also maintained.ConclusionPatients with symptomatic spinal stenosis treated surgically compared to those treated nonoperatively maintain substantially greater improvement in pain and function through 4 years.
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