ArticleBMC medical genomics2025
Single-cell sequencing-based study of ferroptosis mechanisms in heat stroke: identification of key biomarkers and dynamic analysis of the immune microenvironment.
Article in BMC medical genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Ferroptosis in heatstroke: Mechanisms and therapeutic perspectives (Review).International journal of molecular medicine · 2026Review
- Network Pharmacology and Molecular Docking Reveal Myricanone's Role in Alleviating Ischemic Cerebral Infarction via Targeting MAPK14.Biochemical genetics · 2026Article
- Nuclear factor erythroid 2-related factor 2 gene expression in patients with heat stroke and its association with oxidative stress and inflammation: a prospective study.Frontiers in immunology · 2026Article
- Protective Gene Signatures in the Transition from SIRS to Sepsis: Insights from Integrative Transcriptomics and Validation Across Clinical Cohorts.Infection and drug resistance · 2026Article
- The Role ofInfection and drug resistance · 2026Article
- A New Paradigm for Precision Medicine in Heatstroke: From Molecular Subtyping to Targeted Prevention and Treatment.Journal of inflammation research · 2026Review
- Genetic insights into 5-LOX-activating protein: a narrative review of disease associations.Human genomics · 2025Review
- Targeting c-Jun orchestrates heat stroke-induced myocardial injury and reveals its biomarker potential.Frontiers in immunology · 2025Article
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Authors and funding
10 authors.
Funding
Abstract
backgroundHeat stroke, caused by excessive heat production or impaired dissipation, often results from prolonged heat exposure or strenuous activity. Ferroptosis, a novel form of programmed cell death, has been implicated in its pathogenesis, though its mechanisms remain unclear.
objectiveThis study investigates the molecular mechanisms linking heat stroke and ferroptosis using single-cell and transcriptomic analyses to identify diagnostic and therapeutic targets.
methodsPeripheral blood samples from 29 heat stroke patients, recruited at an early stage of the condition, underwent transcriptome sequencing, and single-cell RNA sequencing was conducted for two representative cases. Ferroptosis-related genes were identified by integrating the FerrDB database, followed by weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis to pinpoint ferroptosis-related genes most characteristic of heat stroke. Functional enrichment analyses, including GO and KEGG pathways, were performed. Single-cell RNA sequencing revealed immune microenvironment alterations and marker genes linked to heat stroke pathogenesis. Receiver operating characteristic (ROC) analysis evaluated the diagnostic potential of these genes. Additionally, pseudotime analysis elucidated cell differentiation trajectories and the roles of key genes.
resultsIn Dataset 1, 630 differentially expressed genes (546 up-regulated, 84 down-regulated) and 1,979 heat stroke-related genes were identified. Among them, 14 intersected with 1,001 ferroptosis-related genes and were enriched in pathways like fatty acid metabolism, inflammation, and immune regulation. Single-cell sequencing showed increased monocytes and macrophages in heat stroke patients. Five core genes (ACSL1, MAPK14, ALOX5AP, PROK2, and DUSP1) were validated in Dataset 2 with high AUC values (1.0, 1.0, 0.952, 0.976, and 0.881, respectively). These genes were highly expressed in neutrophils, dendritic cells, and monocytes. Pseudotime analysis confirmed their roles in cell differentiation and disease progression.
conclusionACSL1, MAPK14, ALOX5AP, PROK2, and DUSP1 were identified as novel biomarkers for diagnosing heat stroke. ROC validation confirmed their strong association with the disease, highlighting their potential as diagnostic targets. Pseudotime analysis revealed their consistency in cellular differentiation trajectories.
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