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神经性疼痛背根神经节能量代谢相关图谱的综合转录组生物信息学分析

The Integrated Transcriptome Bioinformatics Analysis of Energy Metabolism-Related Profiles for Dorsal Root Ganglion of Neuropathic Pain.

作者信息

Chen Yongmei, Liu Fan, Shi Shengnan, Xiao Shugen, Gong Xingrui

机构信息

Department of Laboratory, Xiangyang Central Hospital, Affiliation of Hubei University of Art and Science, Xiangyang City, Hubei, China.

Institute of Neuroscience, Department of Anesthesiology, Xiangyang Central Hospital, Affiliation of Hubei University of Art and Science, No.136, Jingzhou Street, Xiangcheng District, Xiangyang City, 441000, Hubei, China.

出版信息

Mol Neurobiol. 2025 Apr;62(4):4149-4171. doi: 10.1007/s12035-024-04537-2. Epub 2024 Oct 15.

Abstract

Neuropathic pain (NP) is a debilitating disease and is associated with energy metabolism alterations. This study aimed to identify energy metabolism-related differentially expressed genes (EMRDEGs) in NP, construct a diagnostic model, and analyze immune cell infiltration and single-cell gene expression characteristics of NP. GSE89224, GSE123919, and GSE134003 were downloaded from the Gene Expression Omnibus. Differentially expressed genes (DEGs) analysis and an intersection with highly energy metabolism-related modules in weighted gene co-expression network analysis (WGCNA) was performed in GSE89224. Least absolute shrinkage and selection operator (LASSO), random forest, and logistic regression were used for model genes selection. NP samples were divided into high- and low-risk groups and different disease subtypes based on risk score of LASSO algorithm and consensus clustering analysis, respectively. Immune cell composition was estimated in different risk groups and NP subtypes. Datasets 134,003 were performed for identification of single-cell DEGs and functional enrichment. Cell-cell communications and pseudo-time analysis to reveal the expression profile of NP. A total of 38 EMRDEGs were obtained and are majorly enriched in metabolism about glioma and inflammation. LASSO, random forest, and logistic regression identified 6 model genes, which were Itpr1, Gng8, Socs3, Fscn1, Cckbr, and Camk1. The nomogram, based on six model genes, had a good predictive ability, concordance, and diagnostic value. The comparisons between different risk groups and NP subtypes identified important pathways and different immune cells component. The immune infiltration results majorly associated with inflammation and energy metabolism. Single-cell analysis revealed cell-cell communications and cells differentiation characteristics of NP. In conclusion, our results not only elucidate the involvement of energy metabolism in NP but also provides a robust diagnostic tool with six model genes. These findings might give insight into the pathogenesis of NP and provide effective therapeutic regimens for the treatment of NP.

摘要

神经性疼痛(NP)是一种使人衰弱的疾病,与能量代谢改变有关。本研究旨在识别NP中与能量代谢相关的差异表达基因(EMRDEGs),构建诊断模型,并分析NP的免疫细胞浸润和单细胞基因表达特征。从基因表达综合数据库下载了GSE89224、GSE123919和GSE134003。在GSE89224中进行了差异表达基因(DEGs)分析,并与加权基因共表达网络分析(WGCNA)中与高能量代谢相关的模块进行了交集分析。使用最小绝对收缩和选择算子(LASSO)、随机森林和逻辑回归进行模型基因选择。根据LASSO算法的风险评分和一致性聚类分析,将NP样本分别分为高风险组和低风险组以及不同的疾病亚型。估计不同风险组和NP亚型中的免疫细胞组成。对数据集134,003进行单细胞DEGs鉴定和功能富集分析。进行细胞间通讯和伪时间分析以揭示NP的表达谱。共获得38个EMRDEGs,主要富集在胶质瘤代谢和炎症方面。LASSO、随机森林和逻辑回归确定了6个模型基因,分别为Itpr1、Gng8、Socs3、Fscn1、Cckbr和Camk1。基于这6个模型基因的列线图具有良好的预测能力、一致性和诊断价值。不同风险组和NP亚型之间的比较确定了重要途径和不同的免疫细胞组成。免疫浸润结果主要与炎症和能量代谢相关。单细胞分析揭示了NP的细胞间通讯和细胞分化特征。总之,我们的结果不仅阐明了能量代谢在NP中的作用,还提供了一个包含6个模型基因的强大诊断工具。这些发现可能有助于深入了解NP的发病机制,并为NP的治疗提供有效的治疗方案。

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