Chen Xiaoyu, Liu Qingquan, Chen Niyao, Ma Jiangxin, Wu Xiaohong, Zhang Haibin, Yu Liying, Huang Huibin
Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Department of Cardiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
J Diabetes. 2024 Mar;16(3):e13506. doi: 10.1111/1753-0407.13506. Epub 2023 Nov 29.
Diabetic peripheral neuropathy (DPN) is a common complication of Type 2 diabetes mellitus (T2DM), which frequently results in disabling neuropathic pain and lower-limb amputation. The identification of noninvasive biomarkers for DPN may help early detection and individualized treatment of DPN.
In this study, we identified differentially expressed genes (DEGs) between DPN and the control based on blood-source (GSE95849) and tissue-source gene expression profiles (GSE143979) from the Gene Expression Omnibus (GEO) database using limma, edgeR, and DESeq2 approaches. KEGGG and GO functional enrichments were performed. Hub genes and their correlation with infiltrating immune cells were analyzed. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to quantify hub gene expression.
In total, 144 DEGs between DPN and the control were identified. Functional enrichment revealed that the DEGs were mainly enriched in immune-related pathways like the Fc epsilon receptor Ig signaling pathway. By protein-protein interaction (PPI) network analysis, FCER1G, SYK, ITGA4, F13A1, MS4A2, and PTK2B were screened as hub genes with higher expression in DPN patients, among which half were immune genes (FCER1G, PTK2B, and SYK). RT-qPCR demonstrated that mRNA expression of FCER1G, PTK2B, and SYK was significantly increased in patients with DPN compared with both diabetic nonperipheral neuropathy (DNN) and normal subjects. The area under the receiver operating characteristic (ROC) curve of FCER1G, PTK2B, and SYK was 0.84, 0.81, and 0.73, respectively, suggesting their great advantages as diagnostic biomarkers to predict the progression of neuropathy in T2DM. Further analysis indicated that the expression of FCER1G, PTK2B, and SYK was negatively correlated with the cell proportion of significantly altered resting natural killer cells, T follicular helper cells, and activated mast cells, but positively correlated with monocytes.
Our findings demonstrated FCER1G, PTK2B, and SYK are potential diagnostic biomarkers and therapeutic targets for DPN, which provides new insight into DPN pathogenesis and therapies.
糖尿病周围神经病变（DPN）是2型糖尿病（T2DM）的常见并发症，常导致致残性神经病理性疼痛和下肢截肢。识别DPN的非侵入性生物标志物可能有助于DPN的早期检测和个体化治疗。
在本研究中，我们使用limma、edgeR和DESeq2方法，基于来自基因表达综合数据库（GEO）的血源（GSE95849）和组织源基因表达谱（GSE143979），确定DPN与对照组之间的差异表达基因（DEG）。进行了KEGG和GO功能富集分析。分析了枢纽基因及其与浸润免疫细胞的相关性。使用实时定量聚合酶链反应（RT-qPCR）对枢纽基因表达进行定量。
共鉴定出DPN与对照组之间的144个DEG。功能富集显示，DEG主要富集于免疫相关途径，如Fcε受体Ig信号通路。通过蛋白质-蛋白质相互作用（PPI）网络分析，筛选出FCER1G、SYK、ITGA4、F13A1、MS4A2和PTK2B作为在DPN患者中表达较高的枢纽基因，其中一半是免疫基因（FCER1G、PTK2B和SYK）。RT-qPCR表明，与糖尿病非周围神经病变（DNN）患者和正常受试者相比，DPN患者中FCER1G、PTK2B和SYK的mRNA表达显著增加。FCER1G、PTK2B和SYK的受试者工作特征（ROC）曲线下面积分别为0.84、0.81和0.73，表明它们作为预测T2DM神经病变进展的诊断生物标志物具有很大优势。进一步分析表明，FCER1G、PTK2B和SYK的表达与显著改变的静息自然杀伤细胞、T滤泡辅助细胞和活化肥大细胞的细胞比例呈负相关，但与单核细胞呈正相关。
我们的研究结果表明，FCER1G、PTK2B和SYK是DPN潜在的诊断生物标志物和治疗靶点，这为DPN的发病机制和治疗提供了新的见解。
