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Published on: December 15, 2023
Identification of PANoptosis-related biomarkers in spinal cord injury (SCI) through multi-omics analysis and machine
Song Xu1, Guozhu Wang1, Xiongwen Zhang1
1Orthopedic Sugery Division One (Spine&Trauma), Sixth Affiliated Hospital of Kunming Medical University, Yuxi, Yunnan, China.
Background:
Spinal cord injury (SCI) is a severe neurological disorder lacking early diagnostic biomarkers and precise therapeutic targets. PANoptosis, a combined cell death process involving apoptosis, necroptosis, and pyroptosis, is implicated in poor functional recovery after SCI, yet its biomarkers remain unexplored. This study aims to identify biomarkers associated with PANoptosis in SCI.
Methods:
Differentially expressed genes (DEGs) associated with SCI were identified using bioinformatics analysis, followed by functional enrichment. Weighted gene co-expression network analysis (WGCNA) and three machine learning algorithms (random forest, LASSO, and SVM-RFE) were used to identify core PANoptosis-related genes. A protein-protein interaction network and a nomogram model were constructed, and immune infiltration was analyzed. Gene expression and function were validated in vitro using an LPS-induced BV2 microglial injury model.
Results:
A total of 1,167 DEGs were identified, mainly enriched in immune and calcium signaling pathways. Five core genes (PPP3CC, DFFB, PSMA6, PRKCQ, and PIK3CB) were identified through integrated analysis. The nomogram showed that higher PIK3CB and PSMA6 expression was associated with increased risk, whereas higher PPP3CC, DFFB, and PRKCQ expression indicated lower risk. These genes were significantly correlated with multiple immune cell subsets. In vitro experiments confirmed altered protein expression after LPS stimulation, with PPP3CC most notably downregulated. PPP3CC overexpression partially restored cell viability and reduced IL-6, IL-1β, and TNF-α levels.
Conclusion:
PANoptosis appears to play a significant role in the pathogenesis of SCI. The identified genes are potential biomarkers of immune regulation, and PPP3CC may serve as a protective factor and therapeutic target.
