Integration of bulk/scRNA-seq and multiple machine learning algorithms identifies PIM1 as a biomarker associated with cuproptosis and ferroptosis in abdominal aortic aneurysm

• Published in: Frontiers in immunology 2024, Vol.15, p.1486209
• Main Authors: Han, Zonglin, Lu, Xiulian, He, Yuxiang, Zhang, Tangshan, Zhou, Zhengtong, Zhang, Jingyong, Zhou, Hua
• Format: Article
• Language: English
• Subjects: abdominal aortic aneurysm; Algorithms; Animals; Aortic Aneurysm, Abdominal - genetics; Biomarkers; Computational Biology - methods; cuproptosis; Disease Models, Animal; ferroptosis; Ferroptosis - genetics; Gene Expression Profiling; Humans; Immunology; Machine Learning; Male; Mice; PIM1; Proto-Oncogene Proteins c-pim-1 - genetics; Proto-Oncogene Proteins c-pim-1 - metabolism; RNA-Seq; Single-Cell Gene Expression Analysis; WGCNA
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1486209

Abdominal aortic aneurysm (AAA) is a serious life-threatening vascular disease, and its ferroptosis/cuproptosis markers have not yet been characterized. This study was aiming to identify markers associated with ferroptosis/cuproptosis in AAA by bioinformatics analysis combined with machine learning models and to perform experimental validation. This study used three scRNA-seq datasets from different mouse models and a human PBMC bulk RNA-seq dataset. Candidate genes were identified by integrated analysis of scRNA-seq, cell communication analysis, monocle pseudo-time analysis, and hdWGCNA analysis. Four machine learning algorithms, LASSO, REF, RF and SVM, were used to construct a prediction model for the PBMC dataset, the above results were comprehensively analyzed, and the targets were confirmed by RT-qPCR. scRNA-seq analysis showed Mo/MF as the most sensitive cell type to AAA, and 34 cuproptosis associated ferroptosis genes were obtained. Pseudo-time series analysis, hdWGCNA and machine learning prediction model construction were performed on these genes. Subsequent comparison of the above results showed that only PIM1 appeared in all algorithms. RT-qPCR and western blot results were consistent with sequencing results, showing that PIM1 was significantly upregulated in AAA. In a conclusion, PIM1 as a novel biomarker associated with cuproptosis/ferroptosis in AAA was highlighted.