Guo Jintao, Sun Tao
Shandong Provincial Hospital, Shandong University, Jinan, 250100, China.
Department of PainManagement, Shandong Provincial Hospital, Shandong University, Jinan, 250001, China.
Sci Rep. 2025 Jul 16;15(1):25767. doi: 10.1038/s41598-025-06756-6.
Chronic low back pain (cLBP ) is a common condition that affects the quality of life, can be caused by disc degeneration, facet arthropathy, myofascial pain, sacroiliac joint pain, spondyloarthropathies, and nociplastic pain etc. Research suggests that excessive pyroptosis may trigger cytokine release and harmful inflammation, leading to tissue damage and organ dysfunction, which could be a potential molecular mechanism underlying these conditions. Our aim in this research was to look into the effects of genes associated with pyroptosis in cLBP, with the goal of describing possible markers for diagnosis and targets for treatment. A comprehensive analysis of Differentially Expressed Genes (DEGs) was performed utilizing the GSE177034 datasets sourced from the Gene Expression Omnibus (GEO) repository. GSE177034 included 98 patients admitted to the hospital for treatment of low back pain, all of whom had peripheral blood extracted and sequenced. We identified 883 DEGs, including 397 upregulated and 486 downregulated genes, in cLBP. The WGCNA revealed 11 co-expression modules, with the blue module presenting the utmost positive connection to pyroptosis. The GO and KEGG analyses showed that DEGs associated with pyroptosis were substantially enriched in pathways like the NF-kappaB transcription factor activity and the MyD88-dependent signaling pathway of Toll-like receptors. Machine learning approaches identified five pyroptosis relate hub genes (AVIL, PADI4, ARHGAP24, ST3GAL6, and BICDL2) as potential biomarkers. The cLBP diagnostic column chart model was established, demonstrating the accuracy of hub genes as biomarkers. A hub mRNA-related interaction network was constructed to identify potential therapeutic drugs, followed by verification of hub gene expression levels to validate their role in cLBP. Moreover, the investigation into immune cell infiltration revealed substantial disparities in the presence of five distinct immune cell types between the chronic LBP and acute LBP cohorts. Specifically, activated effector memory CD8 T cells (R = - 0.5407, p-value < 0.001) ,and CD56bright natural killer cells (R = - 0.5438, p-value < 0.001) were all found to be significantly different. These findings suggest that immune involvement may play a role in the development of cLBP. This study identified diagnostic biomarkers and therapeutic targets for cLBP, offering promising avenues for improved diagnosis and treatment. The identification of specific biomarkers, including AVIL, PADI4, ARHGAP24, ST3GAL6, and BICDL2, enhances diagnostic precision by enabling the stratification of cLBP subtypes based on underlying pathophysiology.
慢性下腰痛（cLBP）是一种常见病症，会影响生活质量，可能由椎间盘退变、小关节病、肌筋膜疼痛、骶髂关节疼痛、脊柱关节病和神经源性疼痛等引起。研究表明，过度的细胞焦亡可能触发细胞因子释放和有害炎症，导致组织损伤和器官功能障碍，这可能是这些病症潜在的分子机制。本研究的目的是探究与cLBP中细胞焦亡相关基因的作用，旨在描述可能的诊断标志物和治疗靶点。利用来自基因表达综合数据库（GEO）库的GSE177034数据集对差异表达基因（DEG）进行了全面分析。GSE177034包括98名因下腰痛入院治疗的患者，所有患者均采集外周血并进行测序。我们在cLBP中鉴定出883个DEG，包括397个上调基因和486个下调基因。加权基因共表达网络分析（WGCNA）揭示了11个共表达模块，其中蓝色模块与细胞焦亡呈现出最强的正相关。基因本体（GO）和京都基因与基因组百科全书（KEGG）分析表明，与细胞焦亡相关的DEG在NF-κB转录因子活性和Toll样受体的MyD88依赖性信号通路等途径中显著富集。机器学习方法确定了五个与细胞焦亡相关的枢纽基因（AVIL、PADI4、ARHGAP24、ST3GAL6和BICDL2）作为潜在生物标志物。建立了cLBP诊断柱状图模型，证明了枢纽基因作为生物标志物的准确性。构建了一个枢纽mRNA相关的相互作用网络以识别潜在治疗药物，随后验证枢纽基因表达水平以确认它们在cLBP中的作用。此外，对免疫细胞浸润的研究揭示了慢性下腰痛和急性下腰痛队列中五种不同免疫细胞类型存在显著差异。具体而言，活化的效应记忆CD8 T细胞（R = -0.5407，p值<0.001）和CD56bright自然杀伤细胞（R = -0.5438，p值<0.001）均存在显著差异。这些发现表明免疫参与可能在cLBP的发生发展中起作用。本研究确定了cLBP的诊断生物标志物和治疗靶点，为改善诊断和治疗提供了有前景的途径。鉴定出包括AVIL、PADI4、ARHGAP24、ST3GAL6和BICDL2在内的特定生物标志物，通过基于潜在病理生理学对cLBP亚型进行分层，提高了诊断精度。
