Kattan Shahad W, Basri Ahmed M, Alhashmi Mohammad H, Almars Amany I, Alhasani Reem Hasaballah, Alsharif Ifat, Sindi Ikhlas A, Mufti Ahmad H, Abumansour Iman S, Elhawary Nasser A, Qahtani Aishah Abdullah, Almohaimeed Hailah M
Medical Laboratory Department, College of Applied Medical Sciences, Taibah University, Yanbu, Saudi Arabia.
Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
J Diabetes Investig. 2025 Aug;16(8):1473-1486. doi: 10.1111/jdi.70026. Epub 2025 Jun 5.
Diabetes is a chronic disease resulting from insufficient insulin secretion or impaired insulin function. Diabetic nephropathy (DN) is one of the most common complications of diabetes and a leading cause of end-stage renal disease. Early diagnosis of DN is crucial for timely intervention and effective disease management.
Gene expression profiles GSE142025 and GSE220226 were retrieved from the GEO database and combined into a metadata cohort, while GSE189007 was obtained as an independent validation dataset. Differentially expressed genes (DEGs) were identified in 46 glomerular samples from DN patients and 31 control samples. Gene Ontology (GO) and Disease Ontology (DO) enrichment analyses, gene set enrichment analysis (GSEA), least absolute shrinkage and selection operator (LASSO) regression, support vector machine-recursive feature elimination (SVM-RFE) analysis, and area under the curve (AUC) calculations were performed.
A total of 109 DEGs were identified. Among them, DUSP1, EGR1, FPR1, G6PC, GDF15, LOX, LPL, PRKAR2B, PTGDS, and TPPP3 were selected as potential diagnostic biomarkers for DN. These biomarkers exhibited a positive correlation with immune cell infiltration. Experimental validation identified LOX as the most promising novel diagnostic biomarker for DN. This study provides new insights into the early diagnosis, pathogenesis, and molecular mechanisms of DN.
糖尿病是一种由于胰岛素分泌不足或胰岛素功能受损导致的慢性疾病。糖尿病肾病（DN）是糖尿病最常见的并发症之一，也是终末期肾病的主要原因。DN的早期诊断对于及时干预和有效管理疾病至关重要。
从基因表达综合数据库（GEO数据库）中检索基因表达谱GSE142025和GSE220226，并将其合并为一个元数据队列，同时获取GSE189007作为独立验证数据集。在46例DN患者的肾小球样本和31例对照样本中鉴定差异表达基因（DEG）。进行基因本体（GO）和疾病本体（DO）富集分析、基因集富集分析（GSEA）、最小绝对收缩和选择算子（LASSO）回归、支持向量机递归特征消除（SVM-RFE）分析以及曲线下面积（AUC）计算。
共鉴定出109个DEG。其中，双特异性磷酸酶1（DUSP1）、早期生长反应蛋白1（EGR1）、甲酰肽受体1（FPR1）、葡萄糖-6-磷酸酶（G6PC）、生长分化因子15（GDF15）、赖氨氧化酶（LOX）、脂蛋白脂肪酶（LPL）、蛋白激酶A调节亚基2β（PRKAR2B）、前列腺素D合成酶（PTGDS）和微管动力蛋白3（TPPP3）被选为DN的潜在诊断生物标志物。这些生物标志物与免疫细胞浸润呈正相关。实验验证确定LOX是DN最有前景的新型诊断生物标志物。本研究为DN的早期诊断、发病机制和分子机制提供了新的见解。
