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ORIGINAL RESEARCH article
Front. Neurol.
Sec. Neurological Biomarkers
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1526966
Identification and Validation of Biomarkers Associated with Mitochondrial Dysfunction and Ferroptosis in Rat Spinal
Provisionally accepted- 1 Department of Orthopaedics, ZhuJiang Hospital of Southern Medical University, Guang Zhou, China
- 2 Department of Orthopaedics, General Hospital of Southern Theatre Command of PLA, Guang Zhou, China
Research indicates that mitochondrial dysfunction and ferroptosis may interact following spinal cord injury (SCI), collectively impacting the survival and repair capability of neuronal cells post-injury. Thus, our work sought to identify biomarkers linked to mitochondria and ferroptosis through bioinformatics. This study identified 2 biomarkers (Hypocretin (Hcrt) and Cell division cycle associated 2 (Cdca2)) associated with mitochondria and ferroptosis in SCI, both of which were highly expressed in SCI samples. Tissue-specific results by genotype-tissue expression (GTEx) database showed that both 2 biomarkers were expressed in the brain -spinal cord. The artificial neural network (ANN) generated based on the 2 biomarkers was accurate in distinguishing SCI samples from control samples. Enrichment analysis revealed that co-enrich pathways for Hcrt and Cdca2 including "ubiquitin mediated proteolysis", "endocytosis "and "neurotrophin signaling pathway". In immune infiltration analysis, Wilcoxon-test revealed remarkable discrepancies in T follicular helper cell between SCI and control samples, with a lower level in the SCI sample.Notably, T follicular helper cell was positively linked to Hcrt and negatively linked to Cdca2. In addition, it was discovered that 7 transcription factors could be found to be co-regulators of Hcrt and Cdca2. With regard to drug prediction, pinosylvin, zinc acetate dihydrate, hydroquinone, lucanthone, and dasatinib were stable in their interactions with Cdca2. Real-time quantitative polymerase chain reaction (RT-qPCR) validation revealed that the expression trends of Hcrt and Cdca2 genes were consistent with the trends observed in the dataset and the differences were statistically significant. The present study identified biomarkers (Hcrt and Cdca2) associated with mitochondria and ferroptosis in SCI rats, which was beneficial in providing novel insights for diagnostic and mechanistic studies of SCI.
Keywords: spinal cord injury, ferroptosis, Mitochondria, biomarker, machine learning
Received: 28 Nov 2024; Accepted: 27 Feb 2025.
Copyright: © 2025 Zhu, Wang, Zhang and Zhou. 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:
Yu Zhang, Department of Orthopaedics, General Hospital of Southern Theatre Command of PLA, Guang Zhou, China
Chusong Zhou, Department of Orthopaedics, ZhuJiang Hospital of Southern Medical University, Guang Zhou, China
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