Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
Hereditas. 2023 Mar 1;160(1):8. doi: 10.1186/s41065-023-00269-w.
Neuropathic pain (NP) is one of the most common types of chronic pain and significantly compromises the quality of life. Autophagy is an intracellular catabolic process that is required to maintain cellular homeostasis in response to various stresses. The role of autophagy-related genes in the diagnosis and treatment of neuropathic pain remains unclear.
We identified autophagy-related differentially expressed genes (ARDEGs) and differentially expressed miRNAs (DE-miRNAs) in neuropathic pain by bioinformatics analysis of the GSE145226 and GSE145199 datasets. These ARDEGs and their co-expressed genes were subjected to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Gene Set Enrichment Analysis (GSEA) and friends analysis. Meanwhile, we constructed TFs-ARDEGs, miRNA-ARDEGs regulatory network through ChIPBase database and the HTFtarget database, multiMir R package. Finally, we performed immune infiltration analysis of ARDEGs by Single Sample Gene Set Enrichment Analysis (ssGSEA).
We identified 2 potential autophagy-related differentially expressed genes (Sirt2 and ST7) that may be closely associated with the pathogenesis of neuropathic pain. GO, KEGG and GSEA analysis revealed that these two ARDEGs were mainly enriched in pyridine nucleotide metabolic process, nicotinamide nucleotide metabolic process, Nicotinate and nicotinamide metabolism, NF-κB pathway, KRAS signaling, P53 pathway. In the TFs-ARDEGs and miRNA-ARDEGs regulatory network, miR-140-5p and Cebpb were predicted to be as crucial regulators in the progression of NP. For the ssGSEA results, Sirt2 was positively correlated with Eosinophil and Effector memory CD8 T cell infiltration, which suggested that it may be involved in the regulation of neuroimmune-related signaling.
Two autophagy-related differentially expressed genes, especially Sirt2, may be potential biomarkers for NP, providing more evidence about the crucial role of autophagy in neuropathic pain.
神经病理性疼痛（NP）是最常见的慢性疼痛类型之一，严重影响生活质量。自噬是一种细胞内分解代谢过程，需要它来响应各种应激以维持细胞内稳态。自噬相关基因在神经病理性疼痛的诊断和治疗中的作用尚不清楚。
我们通过对 GSE145226 和 GSE145199 数据集的生物信息学分析，确定了神经病理性疼痛中的自噬相关差异表达基因（ARDEGs）和差异表达 miRNA（DE-miRNAs）。对这些 ARDEGs 及其共表达基因进行基因本体论（GO）、京都基因与基因组百科全书（KEGG）富集分析、基因集富集分析（GSEA）和朋友分析。同时，我们通过 ChIPBase 数据库和 HTFtarget 数据库构建了 TFs-ARDEGs、miRNA-ARDEGs 调控网络，使用多 Mir R 包。最后，我们通过单样本基因集富集分析（ssGSEA）对 ARDEGs 进行免疫浸润分析。
我们确定了 2 个可能与神经病理性疼痛发病机制密切相关的潜在自噬相关差异表达基因（Sirt2 和 ST7）。GO、KEGG 和 GSEA 分析表明，这两个 ARDEGs 主要富集在吡啶核苷酸代谢过程、烟酰胺核苷酸代谢过程、烟酰胺代谢、NF-κB 通路、KRAS 信号通路、P53 通路。在 TFs-ARDEGs 和 miRNA-ARDEGs 调控网络中，miR-140-5p 和 Cebpb 被预测为 NP 进展的关键调控因子。对于 ssGSEA 结果，Sirt2 与嗜酸性粒细胞和效应记忆 CD8 T 细胞浸润呈正相关，这表明它可能参与神经免疫相关信号的调节。
两个自噬相关差异表达基因，尤其是 Sirt2，可能是 NP 的潜在生物标志物，为自噬在神经病理性疼痛中的关键作用提供了更多证据。
