ORIGINAL RESEARCH article
Front. Mol. Neurosci.
Sec. Molecular Signalling and Pathways
Volume 18 - 2025 | doi: 10.3389/fnmol.2025.1639705
Cross-Disease Biomarker Identification Reveals Shared Diagnostic Biomarkers for IVDD and NAFLD via Bulk and Single-Cell RNA Sequencing
Provisionally accepted
- 1Xinxiang Medical University, Xinxiang, China
- 2Department of Orthopedic Surgery, Shanghai Changzheng Hospital, Huangpu, China
- 3Naval medical center of PLA, Shanghai, Chian, Shanghai, China
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Intervertebral disc degeneration (IVDD) and non-alcoholic fatty liver disease (NAFLD) are significant global health challenges. Recent studies suggest an association between them, but the mechanisms remain unclear. This study aimed to explore their shared molecular landscape using bioinformatics. Three IVDD and two NAFLD datasets were obtained from the Gene Expression Omnibus (GEO). Analyses included differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA), and machine learning to identify shared hub genes. Diagnostic value was validated via ROC curves and nomograms. Six shared genes were identified, with ME1, HAS2, and ADRB2 as potential biomarkers for the two diseases. Validation confirmed their expression patterns and robust predictive abilities. KEGG analysis and immune infiltration analysis revealed the important roles of the three biomarkers in disease-associated pathways and immune cell types. Single-cell sequencing analysis demonstrated the predominant expression, distribution, and function of the three hub genes across cell clusters in intervertebral disc and liver tissues, respectively. In vivo experiments suggested that NAFLD could aggravate the progression of IVDD in vivo, and alleviating NAFLD via swimming showed protective effects on IVDD in the context of HFD. This study underscores ME1, HAS2, and ADRB2 as pivotal biomarkers for IVDD and NAFLD, shedding new light on their molecular interplay and deepening our understanding of these two diseases. This study underscores ME1, HAS2, and ADRB2 as pivotal biomarkers for IVDD and NAFLD, shedding new light on their molecular interplay. These findings also revealed Exercise emerges as a promising therapy for both diseases.
Keywords: Intervertebral Disc Degeneration, Non-alcoholic fatty liver disease, machine learning, Hub genes, Inflammation, Exercise
Received: 16 Jun 2025; Accepted: 29 Aug 2025.
Copyright: © 2025 Wei, Ji, Liu, Yan, Sun, Lin, Xu and Sun. 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: Kaiqiang Sun, Department of Orthopedic Surgery, Shanghai Changzheng Hospital, Huangpu, China
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