Zhang Yumin, Zhou Hui, Liu Juan, Zhou Nan
Department of Geriatric Endocrinology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, China.
Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Front Endocrinol (Lausanne). 2024 Nov 18;15:1437979. doi: 10.3389/fendo.2024.1437979. eCollection 2024.
Diabetic peripheral neuropathy (DPN) is a common chronic complication of diabetes, while the underlying molecular mechanisms are still unclear. The aim of this study was to screen the key genes and the roles of immune infiltration in DPN using bioinformatics analysis.
DPN mice datasets including GSE222778, GSE11343, GSE70852, GSE27382, and GSE34889 were retrieved from the GEO database. Data of human DPN were retrieved from the dbGaP. The differentially expressed genes (DEGs) were selected and further analyzed by using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and Gene Set Enrichment Analysis (GSEA) to find the shared key pathway. Protein-protein interaction networks were built in shared mouse and human DEGs. The hub genes were selected and verified using high- glucose-treated PC12 cells and Schwann cells. The single-sample GSEA (ssGSEA) algorithm was used to analyze the proportions of infiltrating immune cells in human DPN and the subsequent correlations with hub genes.
A total of 323 mouse DEGs and 501 human DEGs were selected, and they were found significantly enriched in immune-related biological functions and pathways. A total of 13 DEGs were found shared in mice and human DPN datasets, and among them, there were 7 hub genes, namely, PLAUR, S100A8, IL7R, CXCL13, SRPX2, CD300LB, and CFI. The expression of Cfi, S100a8, Cxcl13, and Cd300lb was consistently confirmed . The scores of neutrophils and NK CD56bright cells varied most significantly by immune cell infiltration analysis ( < 0.01). Furthermore, the selected hub genes were found to be highly correlated with the immune infiltration.
Our study indicated the importance of immune dysregulations in DPN and identified several hub genes through combined analysis in mice and human DPN samples, thus providing potential diagnostic and therapeutic targets in the future.
糖尿病周围神经病变（DPN）是糖尿病常见的慢性并发症，但其潜在分子机制仍不清楚。本研究旨在通过生物信息学分析筛选DPN中的关键基因及免疫浸润的作用。
从基因表达综合数据库（GEO）中检索DPN小鼠数据集，包括GSE222778、GSE11343、GSE70852、GSE27382和GSE34889。从数据库基因型和 phenotype 数据库（dbGaP）中检索人类DPN数据。选择差异表达基因（DEGs），并通过基因本体论、京都基因与基因组百科全书富集分析和基因集富集分析（GSEA）进一步分析，以找到共同的关键途径。在共享的小鼠和人类DEGs中构建蛋白质-蛋白质相互作用网络。选择枢纽基因，并使用高糖处理的PC12细胞和雪旺细胞进行验证。采用单样本GSEA（ssGSEA）算法分析人类DPN中浸润免疫细胞的比例及其与枢纽基因的后续相关性。
共选择了323个小鼠DEGs和501个人类DEGs，发现它们在免疫相关生物学功能和途径中显著富集。在小鼠和人类DPN数据集中共发现13个DEGs，其中有7个枢纽基因，即PLAUR、S100A8、IL7R、CXCL13、SRPX2、CD300LB和CFI。Cfi、S100a8、Cxcl13和Cd300lb的表达得到一致证实。通过免疫细胞浸润分析，中性粒细胞和NK CD56bright细胞的评分变化最为显著（<0.01）。此外，发现所选枢纽基因与免疫浸润高度相关。
我们的研究表明免疫失调在DPN中的重要性，并通过对小鼠和人类DPN样本的联合分析鉴定了几个枢纽基因，从而为未来提供了潜在的诊断和治疗靶点。
