ORIGINAL RESEARCH article
Front. Mol. Neurosci.
Sec. Molecular Signalling and Pathways
Volume 18 - 2025 | doi: 10.3389/fnmol.2025.1565430
Exploring Hypoxia-Related Genes in Spinal Cord Injury: A Pathway to New Therapeutic Targets
Provisionally accepted
- 1Department of Rehabilitation Medicine, The First Hospital of Jilin University, Changchun, Jilin Province, China
- 2Department of Rehabilitation Medicine, China-Japan Union Hospital, Jilin University, Changchun, Hebei Province, China
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Spinal cord injury (SCI) remains a debilitating condition with limited therapeutic alternatives. We developed a diagnostic model employing LASSO regression and Random Forest algorithms to investigate hypoxia-related genes in SCI, aiming to identify potential therapeutic targets. This model identified Casp6, Pkm, Cxcr4, and Hexa as critical biomarkers, validated through receiver operating characteristic curves, calibration plots, and decision curves and further substantiated by qPCR experiments. Our methodology effectively eliminated batch effects, facilitating cross-dataset comparisons. Among 9,732 altered genes in SCI, 186 were identified as hypoxia-related differentially expressed genes (HRDEGs), significantly associated with SCI pathogenesis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses highlighted their roles in the hypoxia response, notably involving the hypoxia-inducible factor 1 pathway. The diagnostic model demonstrated high accuracy, with an area under the curve exceeding 0.9, confirming Casp6, Pkm, Cxcr4, and Hexa as biomarkers. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) revealed distinct pathways in low- and high-risk SCI groups, suggesting potential clinical stratification. This study constructs a diagnostic model and offers valuable insights into SCI pathogenesis and novel treatment strategies.
Keywords: spinal cord injury, Hypoxia-related differentially expressed genes, Diagnostic model, Functional enrichment analysis, Gene Regulatory Networks
Received: 23 Jan 2025; Accepted: 02 May 2025.
Copyright: © 2025 Cheng, Li, Xu, Ma and Zheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yinhua Zheng, Department of Rehabilitation Medicine, The First Hospital of Jilin University, Changchun, Jilin Province, China
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