Ye Qingqing, Huang Zhensheng, Lu Weicheng, Yan Fang, Zeng Weian, Xie Jingdun, Zhong Weiqiang
State Key Laboratory of Oncology in Southern China, Department of Anesthesiology, Collaborative Innovation for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
Front Neurosci. 2022 Oct 19;16:994575. doi: 10.3389/fnins.2022.994575. eCollection 2022.
Neuropathic pain is a debilitating disease caused by damage or diseases of the somatosensory nervous system. Previous research has indicated potential associations between neuropathic pain and aging. However, the mechanisms by which they are interconnected remain unclear. In this study, we aim to identify the common differentially expressed genes (co-DEGs) between neuropathic pain and aging through integrated bioinformatics methods and further explore the underlying molecular mechanisms.
The microarray datasets GSE24982, GSE63442, and GSE63651 were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and co-DEGs were first identified. Functional enrichment analyses, protein-protein Interaction (PPI) network, module construction and hub genes identification were performed. Immune infiltration analysis was conducted. Targeted transcription factors (TFs), microRNAs (miRNAs) and potential effective drug compounds for hub genes were also predicted.
A total of 563 and 1,250 DEGs of neuropathic pain and aging were screened, respectively. 16 genes were further identified as co-DEGs. The functional analysis emphasizes the vital roles of the humoral immune response and complement and coagulation cascades in these two diseases. Cxcl14, Fblim1, RT1-Da, Serping1, Cfd, and Fcgr2b were identified as hub genes. Activated B cell, mast cell, activated dendritic cell, CD56 bright natural killer cell, effector memory CD8 + T cell, and type 2 T helper cell were significantly up-regulated in the pain and aging condition. Importantly, hub genes were found to correlate with the activated B cell, activated dendritic cell, Gamma delta T cell, central memory CD4 + T cell and mast cell in pain and aging diseases. Finally, Spic, miR-883-5p, and miR-363-5p et al. were predicted as the potential vital regulators for hub genes. Aldesleukin, Valziflocept, MGD-010, Cinryze, and Rhucin were the potential effective drugs in neuropathic pain and aging.
This study identified co-DEGs, revealed molecular mechanisms, demonstrated the immune microenvironment, and predicted the possible TFs, miRNAs regulation networks and new drug targets for neuropathic pain and aging, providing novel insights into further research.
神经性疼痛是一种由躯体感觉神经系统损伤或疾病引起的使人衰弱的疾病。先前的研究表明神经性疼痛与衰老之间存在潜在关联。然而，它们相互关联的机制仍不清楚。在本研究中，我们旨在通过综合生物信息学方法确定神经性疼痛和衰老之间的共同差异表达基因（共DEGs），并进一步探索潜在的分子机制。
从基因表达综合数据库（GEO）下载微阵列数据集GSE24982、GSE63442和GSE63651。首先鉴定差异表达基因（DEGs）和共DEGs。进行功能富集分析、蛋白质-蛋白质相互作用（PPI）网络、模块构建和枢纽基因鉴定。进行免疫浸润分析。还预测了枢纽基因的靶向转录因子（TFs）、微小RNA（miRNAs）和潜在的有效药物化合物。
分别筛选出563个神经性疼痛的DEGs和1250个衰老的DEGs。进一步鉴定出16个基因作为共DEGs。功能分析强调了体液免疫反应以及补体和凝血级联在这两种疾病中的重要作用。Cxcl14、Fblim1、RT1-Da、Serping1、Cfd和Fcgr2b被鉴定为枢纽基因。在疼痛和衰老状态下，活化B细胞、肥大细胞、活化树突状细胞、CD56明亮自然杀伤细胞、效应记忆CD8 + T细胞和2型辅助性T细胞显著上调。重要的是，发现在疼痛和衰老疾病中枢纽基因与活化B细胞、活化树突状细胞、γδT细胞、中枢记忆CD4 + T细胞和肥大细胞相关。最后，预测Spic、miR-883-5p和miR-363-5p等是枢纽基因的潜在重要调节因子。白细胞介素、Valziflocept、MGD-010、Cinryze和Rhucin是神经性疼痛和衰老中的潜在有效药物。
本研究鉴定了共DEGs，揭示了分子机制，展示了免疫微环境，并预测了神经性疼痛和衰老可能的TFs、miRNAs调控网络及新的药物靶点，为进一步研究提供了新的见解。
