Abstract
Objective: Sciatica pertains to neuropathic pain that has been associated with inflammatory response. We aimed to identify significant immune-related biomarkers for sciatica in peripheral blood. Methods: We utilized the GSE150408 expression profiling data from the Gene Expression Omnibus (GEO) database as the training dataset and extracted immune-related genes for further analysis. Differentially expressed immune-related genes (DEIRGs) between healthy controls and patients with sciatica were selected using the “limma” package and verified in clinical specimens by quantitative reverse transcription PCR (RT-qPCR). A diagnostic immune-related gene signature was established using the training model and random forest (RF), generalized linear model (GLM), and support vector machine (SVM) models. Sciatica patient subtypes were identified using the consensus clustering method. Results: Thirteen significant DEIRGs were acquired, of which five (CRP, EREG, FAM19A4, RLN1, and WFIKKN1) were selected to establish a diagnostic immune-related gene signature according to the most appropriate training model, namely, the RF model. A clinical application nomogram model was established based on the expression level of the five DEIRGs. The sciatica patients were divided into two subtypes (C1 and C2) according to the consensus clustering method. Conclusions: Our research established a diagnostic five immune-related gene signature to discriminate sciatica and identified two sciatica subtypes, which may be beneficial to the clinical diagnosis and treatment of sciatica.
Highlights
Sciatica is a common clinical syndrome caused by irritation of the sciatic nerve and consists of two types: spinal and extra-spinal (Ailianou et al, 2012)
A total of 212 differentially expressed genes (DEGs) between sciatica patients and healthy controls were obtained based on the inclusion criteria log|FC| > 0.2 and p < 0.001
AZU1, BPI, TCF7L2, and WFIKKN1 were upregulated in sciatica patients compared with healthy controls, whereas ANGPTL4, C-reactive protein (CRP), EREG, FAM19A4, FGF1, LOC100129216, PLXNB1, RLN1, and RXFP2 were downregulated
Summary
Sciatica is a common clinical syndrome caused by irritation of the sciatic nerve and consists of two types: spinal and extra-spinal (Ailianou et al, 2012). Sciatica is diagnosed mainly based on history and physical examination. A history of leg pain more intense than back pain or pain below the knee should raise suspicion of sciatica. Inquiries relating to onset and distribution of pain and associated symptoms such as tingling sensation, numbness, or muscle weakness in the legs are helpful (Jensen et al, 2019). A recent cohort study proposed clinical criteria for unilateral leg pain, monoradicular distribution of pain, positive straight leg raise test at
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