分子标志物的挖掘与鉴定对糖尿病健康管理的研究

Mining and Identification of Molecular Markers for Diabetes Health Management

摘要: 背景：糖尿病视网膜病变(DR)是糖尿病最主要的致盲性并发症，其早期诊断困难且缺乏有效的干预靶点，构成了全球性的健康管理挑战。前体mRNA加工因子4B (PRPF4B)在其他糖尿病并发症中扮演关键角色，但其在DR中的作用尚不明确。方法：本研究采用生物信息学分析方法，整合GEO数据库中的GSE185011和GSE146615两个DR数据集。通过批次效应校正、差异表达基因(DEGs)筛选、加权基因共表达网络分析(WGCNA)、蛋白质–蛋白质相互作用(PPI)网络构建以及功能富集分析，筛选DR的核心枢纽基因。并利用CTD数据库和TargetScan平台分析核心基因的疾病关联及上游调控机制。结果：共鉴定出1598个DEGs。WGCNA与PPI网络分析联合筛选出9个核心枢纽基因，其中PRPF4B在DR组织中显著高表达。功能分析表明，PRPF4B与炎症反应、纤维化等DR核心病理过程密切相关。CTD分析进一步证实其与肾脏疾病、纤维化等并发症相关。TargetScan预测其表达可能受hsa-miR-139-5p调控。结论：PRPF4B是DR中一个关键的高表达基因，可能通过调控剪接过程介导炎症和纤维化，从而推动疾病进展。PRPF4B作为一个潜在的生物标志物，其在DR诊断、预后和治疗中的潜力值得进一步研究。

Abstract: Background: Diabetic retinopathy (DR) is the leading cause of blindness in patients with diabetes mellitus. The difficulty in early diagnosis and the lack of effective intervention targets pose a global health challenge. Precursor mRNA processing factor 4B (PRPF4B) plays a key role in other diabetic complications, but its role in DR remains unclear. Methods: Two DR Datasets (GSE185011 and GSE146615) from GEO database were integrated using bioinformatics analysis. The core hub genes of DR were screened by batch effect correction, differentially expressed genes (DEGs) screening, weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network construction and functional enrichment analysis. The CTD database and TargetScan platform were used to analyze the disease association and upstream regulatory mechanism of core genes. Results: A total of 1598 DEGs were identified. WGCNA combined with PPI network analysis screened out 9 core hub genes, among which PRPF4B was significantly highly expressed in DR Tissues. Functional analysis showed that PRPF4B was closely related to inflammatory response, fibrosis and other core pathological processes of DR. CTD analysis further confirmed its association with complications such as kidney disease and fibrosis. TargetScan predicted that its expression may be regulated by hsa-miR-139-5p. Conclusions: PRPF4B is a key highly expressed gene in DR, which may mediate inflammation and fibrosis by regulating the splicing process, thereby promoting the progression of DR. As a potential biomarker, PRPF4B deserves further investigation for its potential in the diagnosis, prognosis and treatment of DR.