Decreased Expression of ENPP6 Predicts the Occurrence of Pain in Malignant Spinal Tumour

Abstract

Background: Neuropathic pain (NeP) characterized by neuroplasticity and neuroinflammatory change is a common complication associated with spinal metastasis. However, there are no reliable candidates for diagnosis and treatment. Recently, cancer research has incorporated molecules into the treatment of patients with NeP, therefore, it is necessary to find key molecules of NeP to provide new targets for diagnosis and treatment.Methods: We analyzed RNA-seq data around the expression of ENPP6 based on bioinformatic methods, including differentially expressed genes (DEGs), Gene Ontology (GO), protein-protein interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG) and GSEA analyses, receiver operating characteristic (ROC) curve, immune cell infiltration and mutation analysis.Results: We divided with pain samples into the High and Low ENPP6 expression groups. A total of 231 DEGs were identified. GO and KEGG analysis showed that DEGs were mainly enriched in Inflammation and cancer associated pathways. GSEA analysis showed that DEGs was significantly enriched in ARF3 and P38/MK2, RHO and RAS, and BRAFT and AKT1/E17K pathway. Pearson’s correlation analysis showed that the expression of ENPP6 was significantly correlated with autophagy phenotype and immunophenotype. Immune infiltrating analysis showed that activated NK cells were significantly highly expressed in Low group. ROC analysis of ENPP6 suggested that the area under the ROC curve was 0.925. Mutation sites analysis showed that most of the mutations in ENPP4-7 were phosphorylation sites.Conclusion: This study provides novel insights into molecular mechanisms underlying NeP, and identifying ENPP6 may serve as potentially diagnostic biomarkers and/or therapeutic targets for NeP.