School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P.R. China.
College of Pharmacy, Guangxi University of Chinese Medicine, Qingxiu, Nanning, Guangxi 530200, P.R. China.
Mol Med Rep. 2024 Sep;30(3). doi: 10.3892/mmr.2024.13279. Epub 2024 Jul 4.
The incidence of Alzheimer's disease (AD) is rising globally, yet its treatment and prediction of this condition remain challenging due to the complex pathophysiological mechanisms associated with it. Consequently, the objective of the present study was to analyze and characterize the molecular mechanisms underlying ferroptosis‑related genes (FEGs) in the pathogenesis of AD, as well as to construct a prognostic model. The findings will provide new insights for the future diagnosis and treatment of AD. First, the AD dataset GSE33000 from the Gene Expression Omnibus database and the FEGs from FerrDB were obtained. Next, unsupervised cluster analysis was used to obtain the FEGs that were most relevant to AD. Subsequently, enrichment analyses were performed on the FEGs to explore biological functions. Subsequently, the role of these genes in the immune microenvironment was elucidated through CIBERSORT. Then, the optimal machine learning was selected by comparing the performance of different machine learning models. To validate the prediction efficiency, the models were validated using nomograms, calibration curves, decision curve analysis and external datasets. Furthermore, the expression of FEGs between different groups was verified using reverse transcription quantitative PCR and western blot analysis. In AD, alterations in the expression of FEGs affect the aggregation and infiltration of certain immune cells. This indicated that the occurrence of AD is strongly associated with immune infiltration. Finally, the most appropriate machine learning models were selected, and AD diagnostic models and nomograms were built. The present study provided novel insights that enhance understanding with regard to the molecular mechanism of action of FEGs in AD. Moreover, the present study provided biomarkers that may facilitate the diagnosis of AD.
阿尔茨海默病(AD)的发病率在全球范围内呈上升趋势,但由于其与复杂的病理生理机制相关,因此该病的治疗和预测仍然具有挑战性。因此,本研究旨在分析和描述与铁死亡相关基因(FEG)在 AD 发病机制中的分子机制,并构建一个预测模型。这些发现将为 AD 的未来诊断和治疗提供新的思路。首先,从基因表达综合数据库(GEO)中获取 AD 数据集 GSE33000 和 FerrDB 中的 FEG。接下来,采用无监督聚类分析获得与 AD 最相关的 FEG。然后,对 FEG 进行富集分析以探讨其生物学功能。随后,通过 CIBERSORT 阐明这些基因在免疫微环境中的作用。然后,通过比较不同机器学习模型的性能,选择最佳的机器学习。为了验证预测效率,使用列线图、校准曲线、决策曲线分析和外部数据集对模型进行验证。此外,通过逆转录定量 PCR 和 Western blot 分析验证不同组之间 FEG 的表达。在 AD 中,FEG 表达的改变影响某些免疫细胞的聚集和浸润。这表明 AD 的发生与免疫浸润密切相关。最后,选择最合适的机器学习模型,并构建 AD 诊断模型和列线图。本研究提供了新的见解,增强了对 FEG 在 AD 中作用机制的理解。此外,本研究提供了可能有助于 AD 诊断的生物标志物。