Molecular characterization of PANoptosis-related genes as novel signatures for peripheral nerve injury based on time-series transcriptome sequencing

Abstract

Programmed cell death (PCD) pathways play pivotal roles in the development and progression of peripheral nerve injury (PNI). PANoptosis, as a novel form of PCD pathway with key features of pyroptosis, apoptosis and necroptosis, is implicated in the pathogenesis of multiple neurologic diseases. This study aimed to identify PANoptosisrelated biomarkers and characterize their molecular roles and immune landscape in PNI. PANoptosis-related genes (PRGs) were retrieved from Reactome pathway database and previous literatures. Differentially expressed PANoptosis-related genes (DEPRGs) were identified based on a time-series transcriptome sequencing dataset. DEPRGs were predicted to be enriched in inflammatory response, inflammatory complex, PCD and NOD-like receptor signaling pathway through GO, KEGG, Reactome and GSEA analysis. Hub genes, including Ripk3, Pycard and Il18, were then recognized through PPI network and multiple algorithms. The molecular regulatory mechanisms of hub genes were elucidated by transcription factor network and competing endogenous RNA network. Moreover, the immune cell landscape of hub genes was analyzed. Eventually, the expression levels of hub genes were verified through external dataset and animal model. Ripk3, Pycard and Il18 were remarkably upregulated in PNI samples, which were in consistent with the results of bioinformatic analysis. This study uncovered the molecular characterization of PANoptosis-related genes in PNI and illustrated the novel PANoptosis biomarker for PNI.