Introduction: SPECT/CT is emerging as a diagnostic tool for identifying pain generators in degenerative spine disease (DSD). Little is known regarding the biological processes that contribute to increased SPECT/CT uptake. Understanding the genetic and molecular mechanisms underpinning this diagnostic tool and by extension DSD may provide important insights into identification of pain generators and surgical planning. Here, we sought to identify differential gene expression between regions of normal SPECT/CT uptake and regions with increased uptake in the spine.
Methods: Patients with DSD and regions of increased SPECT/CT technetium 99 who underwent spinal decompression or fusion surgery at the level with increased uptake were enrolled. Vertebral bone samples were collected intraoperatively from the region with increased uptake and control samples from regions without increased uptake from the same patients. The samples underwent processing and bulk RNA was extracted. The isolated mRNA was sequenced using NovaSeq 6000 RNA Sequencing System. Gene Ontology analysis was performed to evaluate relative gene expression in regions of increased SPECT/CT uptake compared to the control samples. Pathway analysis was performed on the differentially expressed genes to identify differential regulation in canonical pathways involved in bone metabolism and inflammation.
Results: Six experimental samples and five control samples were collected from five patients. Gene Ontology analysis identified genes from several pathways that were significantly up- or down-regulated. The upregulated pathways included thermogenesis, oxidative phosphorylation, and CAMP signaling, among others. Downregulated pathways include osteoclast differentiation, chemokine signaling, protein digestion/absorption, and signal transduction (RAS, MAPK, Wnt), among others.
Conclusion : Regions of increased SPECT/CT uptake demonstrated differential relative gene expression compared to control samples. The differentially expressed genes were implicated in signaling pathways potentially important in bone metabolism and postsurgical inflammation. Further analysis examining the impact of these differences on patient outcomes may have important implications on surgical planning and patient selection.
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