Qin Qiangqiang, Gu Zhanfeng, Li Fei, Pan Yanbing, Zhang TianXiang, Fang Yang, Zhang Lesha
Second Institute of Clinical Medicine, Anhui Medical University, Hefei, China.
Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
Front Aging Neurosci. 2022 May 12;14:881890. doi: 10.3389/fnagi.2022.881890. eCollection 2022.
Alzheimer's disease (AD) is a common neurodegenerative disease. The major problems that exist in the diagnosis of AD include the costly examinations and the high-invasive sampling tissue. Therefore, it would be advantageous to develop blood biomarkers. Because AD's pathological process is considered tightly related to autophagy; thus, a diagnostic model for AD based on ATGs may have more predictive accuracy than other models. We obtained GSE63060 dataset from the GEO database, ATGs from the HADb and screened 64 differentially expressed autophagy-related genes (DE-ATGs). We then applied them to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses as well as DisGeNET and PaGenBase enrichment analyses. By using the univariate analysis, least absolute shrinkage and selection operator (LASSO) regression method and the multivariable logistic regression, nine DE-ATGs were identified as biomarkers, which are , , , , , , , , and . We combined them with sex and age to establish a nomogram model. To evaluate the model's distinguishability, consistency, and clinical applicability, we applied the receiver operating characteristic (ROC) curve, C-index, calibration curve, and on the validation datasets GSE63061, GSE54536, GSE22255, and GSE151371 from GEO database. The results show that our model demonstrates good prediction performance. This AD diagnosis model may benefit both clinical work and mechanistic research.
阿尔茨海默病(AD)是一种常见的神经退行性疾病。AD诊断中存在的主要问题包括检查费用高昂以及组织采样具有高侵入性。因此,开发血液生物标志物将具有优势。由于AD的病理过程被认为与自噬密切相关;因此,基于自噬相关基因(ATGs)的AD诊断模型可能比其他模型具有更高的预测准确性。我们从基因表达综合数据库(GEO数据库)获取了GSE63060数据集,从人类自噬数据库(HADb)获取了ATGs,并筛选出64个差异表达的自噬相关基因(DE - ATGs)。然后我们将它们应用于基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析以及疾病基因网络(DisGeNET)和泛基因库(PaGenBase)富集分析。通过单变量分析、最小绝对收缩和选择算子(LASSO)回归方法以及多变量逻辑回归,确定了9个DE - ATGs作为生物标志物,它们分别是 、 、 、 、 、 、 、 和 。我们将它们与性别和年龄相结合,建立了一个列线图模型。为了评估该模型的区分能力、一致性和临床适用性,我们在来自GEO数据库的验证数据集GSE63061、GSE54536、GSE22255和GSE151371上应用了受试者工作特征(ROC)曲线、C指数、校准曲线。结果表明,我们的模型具有良好的预测性能。这种AD诊断模型可能对临床工作和机制研究都有益处。