Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (6): 2643-2657.doi: 10.4103/NRR.NRR-D-24-00693

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Integrating bulk and single-cell transcriptome profiling to uncover diagnostic biomarkers and regulatory mechanisms in oxidative stress of spinal cord injury

Jianfeng Li1, 2, #, Kuileung Tong3, #, Jiaxiang Zhou1, 2, #, Shiming Li4, Zhongyuan He5, Fuan Wang1, 2, Hongkun Chen1, 2, Haizhen Li1, 2, Gang Cheng6, Junhong Li1, 2, *, Zhiyu Zhou1, 2, *, Manman Gao2, 7, 8, 9, *   

  1. 1Innovation Platform of Regeneration and Repair of Spinal Cord and Nerve Injury, Department of Orthopedics, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, China;  2Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Orthopedic Research Institute/Department of Spinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China;  3Department of Orthopedics, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China;  4Department of Orthopedic Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou, Jiangsu Province, China;  5Department of Orthopedics, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China;  6Department of Orthopedics and Trauma, The Affiliated Hospital of Yunnan University, Yunnan University, Kunming, Yunnan Province, China;  7Orthopedic Research Institute, Fuzhou Second General Hospital, Fuzhou, Fujian Province, China;  8Department of Pediatric Orthopedic, Fuzhou Second General Hospital, Fuzhou, Fujian Province, China;  9Fujian Provincial Clinical Medical Research Center for First Aid and Rehabilitation in Orthopaedic Trauma (2020Y2014), Fuzhou Second General Hospital, Fuzhou, Fujian Province, China
  • Online:2026-06-15 Published:2026-04-18
  • Contact: Manman Gao, PhD, gaomanm@mail2.sysu.edu.cn; Zhiyu Zhou, PhD, zhouzhy23@mail.sysu.edu.cn; Junhong Li, PhD, lijh366@mail2.sysu.edu.cn.
  • Supported by:
    This study was supported by Shenzhen Science and Technology Program, No. JCYJ20230807110259002 (to JL); and The Seventh Affiliated Hospital of Sun Yat-sen University, No. ZSQYRSFPD0050 (to JL); and The Postdoctoral Fellowship Program of CPSF, No. GZC20242074 (to KT).

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Abstract: Oxidative stress significantly contributes to secondary damage after spinal cord injury. Despite its importance, research on oxidative stress in spinal cord injury remains limited. Investigating the expression and regulation of oxidative stress–related genes could enhance the diagnosis and treatment of spinal cord injury. In this study, we analyzed the sequencing data of human blood samples and injured mouse spinal cord tissue that were sourced from GEO databases and identified diagnostic biomarkers associated with the severity of spinal cord injury. We also explored the expression patterns of oxidative stress–related genes, potential regulatory mechanisms, and therapeutic drugs. To validate our findings, we performed immunofluorescence and quantitative polymerase chain reaction to assess gene expression in the injured spinal cord. Our results revealed biomarkers associated with oxidative stress and immune responses across different levels of spinal cord injury in humans. We identified differentially expressed oxidative stress–related genes and key hub genes in injured mouse spinal cord tissue and revealed their temporal expression patterns at both the tissue and single-cell levels. We also clarified the signaling pathways associated with oxidative stress and identified ligand-receptor pairs among various cell types at different time points after injury. Furthermore, we discovered microRNAs, long non-coding RNAs, and transcription factors that regulate these hub genes and revealed their roles in modulating gene expression at various stages after spinal cord injury. We also identified drugs targeting these hub genes. The findings from this study not only aid in identifying diagnostic biomarkers that reflect the severity of spinal cord injury, but also provide insights into the expression dynamics of oxidative stress-related genes. In addition, the study reveals potential regulatory mechanisms and identifies potential drugs to treat patients with spinal cord injury.

Key words: bioinformatics analysis, diagnostic biomarker, drug intervention, expression characteristics, immune change, oxidative stress, regulation mechanism, severity of the illness, spinal cord injury, spinal cord repair