Li Guo-Dong, Li Juan, Fan Jia-Qi, Li Jun-Yi, Zhao Bin, Chen Xiao
Department of Pulmonary and Critical Care Medicine, The Affiliated Tai'an City Central Hospital of Qingdao University, Longtan Road 29#, Tai'an, 271000, China.
Department of Comprehensive Ward, The Affiliated Tai'an City Central Hospital of Qingdao University, Tai'an, China.
Sci Rep. 2025 Apr 26;15(1):14622. doi: 10.1038/s41598-025-98490-2.
Emerging evidence suggests that N6-methyladenosine (m6A) modification significantly influences lung injury, lung cancer, and immune responses. The current study explores the potential involvement of m6A modification in the development of IPF. This research analyzed the GSE93606 dataset of 20 non-IPF and 154 IPF patients, identifying 26 m6A regulators and developing predictive models with RF and SVM, assessed via ROC curves. A nomogram was created with selected m6A factors, including molecular subtyping, PCA for m6A features, immune cell analysis, DEG identification, and functional enrichment. In vitro experiments on MRC-5 cells used RT-qPCR and Western blotting, and virtual drug screening targeted the WTAP protein through molecular docking. Analysis revealed 26 differential m6A regulators in IPF patients, with 16 significant; IGFBP2 and YTHDF2 were overexpressed, while others decreased. RF and SVM models identified predictive m6A regulators, and a nomogram was developed using five factors to predict IPF incidence. Distinct m6A patterns showed changes in RNA levels of specific genes in the BLM-induced group, and five compounds targeting WTAP were identified. This research explored m6A factors' impact on IPF diagnosis and prognosis, identifying WTAP as a potential biomarker.
新出现的证据表明,N6-甲基腺苷(m6A)修饰显著影响肺损伤、肺癌和免疫反应。本研究探讨了m6A修饰在特发性肺纤维化(IPF)发生发展中的潜在作用。本研究分析了20例非IPF患者和154例IPF患者的GSE93606数据集,鉴定出26个m6A调节因子,并使用随机森林(RF)和支持向量机(SVM)建立预测模型,通过ROC曲线进行评估。利用选定的m6A因子创建了列线图,包括分子亚型分析、m6A特征的主成分分析、免疫细胞分析、差异表达基因(DEG)鉴定和功能富集分析。对MRC-5细胞进行的体外实验采用了逆转录定量聚合酶链反应(RT-qPCR)和蛋白质免疫印迹法,通过分子对接对WTAP蛋白进行虚拟药物筛选。分析显示IPF患者中有26个差异m6A调节因子,其中16个具有显著性;胰岛素样生长因子结合蛋白2(IGFBP2)和YTH结构域含蛋白2(YTHDF)过度表达,而其他因子表达降低。RF和SVM模型鉴定出具有预测性的m6A调节因子,并利用五个因子建立列线图来预测IPF的发病率。不同的m6A模式显示博来霉素诱导组中特定基因的RNA水平发生变化,并鉴定出五种靶向WTAP的化合物。本研究探讨了m6A因子对IPF诊断和预后的影响,确定WTAP为潜在的生物标志物。