Characteristics and Significance of Gene Expression Changes in Peripheral Blood of Lumbar Disc Extrusion Patients before and after Nonoperative Treatment

  Objective  To define the gene expression characteristics in the peripheral blood of patients with lumbar disc extrusion (LDE) and the effect of nonoperative treatment on the gene expression.

  Methods  DNA microarray was used to identify semi-quantitatively the differentially expressed genes (DEGs) in the peripheral blood of patients with LDE and that of the healthy controls and the variation trend of these DEGs after nonoperative treatment. Enrichment analysis was done to reveal the functional characteristics of these DEGs, and network analysis was done to identify key genes that contribute to gene dysregulation. The levels of these key genes were measured by qRT-PCR to examine their expression in LDE patients and the controls, and the effect of nonoperative treatment on the expression level.

  Results  We identified 153 DEGs in the peripheral blood of LDE patients and healthy controls, including 131 upregulated genes and 22 downregulated genes. Enrichment analysis revealed that most of the DEGs were related to immunity and the inflammatory response. Network analysis revealed that toll-like receptor 4 (TLR4), matrix metallopeptidase 9 (MMP9) and myeloperoxidase (MPO), cathelicidin antimicrobial peptide (CAMP), resistin (RETN), toll-like receptor 5 (TLR5) were the key genes in the protein-protein interaction network. These key genes were all enriched into the terms releated to immunity and the inflammatory response. The patients experienced pain relief after nonoperative treatment. Among the 153 DEGs, TLR5 , interleukin 1 receptor antagonist (IL1RN) and solute carrier family 8 member A1 (SLC8A1) were downregulated after nonoperative treatment. qRT-PCR revealed that the levels of TLR4, MMP9, MPO, CAMP, RETN, TLR5, IL1RN and SLC8A1 in the peripheral blood of the LDE patients were higher than those of the healthy control group (P<0.05). In addition, TLR5, IL1RN and SLC8A1 expression levels decreased after treatmentin in comparison with the levels before treatment (P<0.05).

  Conclusion  Gene expression in the peripheral blood of LDE patients was characterized by the dysregulation of immune and inflammatory response-related genes, among which, TLR4, MMP9, MPO, CAMP, RETN and TLR5, the genes relevant to immune and inflammatory response, played a key role in the dysregulation of gene expression in the peripheral blood of LDE patients. The outcome of non-operative treatment may be related to the downregulation of the overexpressed TLR5, IL1RN and SLC8A1 in the peripheral blood of patients.