Integrating Single-Cell Sequencing and Transcriptome Analysis to Investigate the Role of Ferroptosis in Ischemic Stroke and the Molecular Mechanisms of Immune Checkpoints.
Weidong Han, Xiaonan Bian, Haiyang Fu, Min Liu, Hongliang Wang, Haimei Liu
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引用次数: 0
Abstract
Background: Early diagnosis of ischemic stroke remains challenging. Given the crucial role of ferroptosis in ischemic stroke, this study aims to identify key genes associated with ferroptosis in ischemic stroke, providing insights into its molecular mechanisms and potential biomarkers for early detection.
Method: The single-cell transcriptome dataset GSE247474 from the Gene Expression Omnibus.Ferroptosis scores in astrocytes were calculated using the WP_FERROPTOSIS gene set, and differential analysis was conducted to compare ferroptosis activity between the disease and control groups. Key ferroptosis-related genes were identified using Lasso regression and support vector machine algorithms, and their diagnostic potential was assessed through ROC curve analysis. Additionally, we performed immune infiltration analysis and transcription factor network prediction. Pseudotime analysis was used to explore the differentiation trajectories of astrocytes and T cell subsets.
Results: Astrocytes in the disease group showed significantly higher ferroptosis scores than those in the control group. Using machine learning algorithms, we identified three key ferroptosis-related genes-SLC3A2 (solute carrier family 3 member 2), FDFT1 (squalene synthase), and BACH1 (BTB and CNC homology 1)-and validated their diagnostic value (AUC > 0.9). Immune infiltration analysis revealed that SLC3A2 and BACH1 expression levels were positively correlated with CD4+ follicular T cells and negatively correlated with CD4+ memory T cells. FDFT1 showed positive correlations with both mast cells and CD4+ memory T cells. Pseudotime analysis demonstrated dynamic changes in key gene expression along the differentiation trajectories of astrocytes and T cells.
Conclusion: SLC3A2, FDFT1, and BACH1 are potential molecular markers for IS diagnosis.
期刊介绍:
World Neurosurgery has an open access mirror journal World Neurosurgery: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review.
The journal''s mission is to:
-To provide a first-class international forum and a 2-way conduit for dialogue that is relevant to neurosurgeons and providers who care for neurosurgery patients. The categories of the exchanged information include clinical and basic science, as well as global information that provide social, political, educational, economic, cultural or societal insights and knowledge that are of significance and relevance to worldwide neurosurgery patient care.
-To act as a primary intellectual catalyst for the stimulation of creativity, the creation of new knowledge, and the enhancement of quality neurosurgical care worldwide.
-To provide a forum for communication that enriches the lives of all neurosurgeons and their colleagues; and, in so doing, enriches the lives of their patients.
Topics to be addressed in World Neurosurgery include: EDUCATION, ECONOMICS, RESEARCH, POLITICS, HISTORY, CULTURE, CLINICAL SCIENCE, LABORATORY SCIENCE, TECHNOLOGY, OPERATIVE TECHNIQUES, CLINICAL IMAGES, VIDEOS