Serum Biomarkers Discovered by SomaScan in Patients with Severe Low Back Pain

Abstract Low back pain is a common clinical problem. Although imaging studies are widely used to evaluate back pain, the link between low back pain and intervertebral disc (IVD) degeneration on images is unclear in many cases 1. Biomarkers for discogenic pain have been examined with candidate marker approaches in the past 2. In this study, we used a proteomic approach to examine 1512 serum proteins. Biomarkers identified include molecules known to correlate with back pain, as well as novel molecules. Biomarker signatures discovered clearly distinguish patients with low back pain from normal controls. Further, a comparison of back pain patients < 40 years of age and similarly aged healthy controls showed that inflammation-related pathways were upregulated in the patients, with leukocyte proliferation pathway the most enriched, and STAT3 (signal transducer and activator of transcription 3) showing the largest number of protein-protein interactions. Among the downregulated biomarkers comparing these two cohorts, SMAD protein phosphorylation pathway was the most enriched, and IL6 (interleukin 6) the most connected. Markers in older back pain patients ≥ 40 years of age differed from younger patients in immune-related pathways, while CD36 (cluster of differentiation 36) has the most interactions with other proteins. Overrepresented pathways and proteins with the largest network connections may be effective treatment targets. Future work includes studying these differences in a larger case-controlled population, expanding the number of proteins considered, and completing a confirmative, quantitative assay for key markers. Following up with patients for their function and pain level would further confirm the diagnostic and prognostic values of the biomarkers identified.