ArticleDiabetology & metabolic syndrome2025
Sphingolipid metabolism-related genes for the diagnosis of metabolic syndrome by integrated bioinformatics analysis and Mendelian randomization identification.
Article in Diabetology & metabolic syndrome, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- The role of classical protein tyrosine phosphatases in diabetic kidney disease and therapeutic implications.Journal of biomedical science · 2026Review
- PTPN18 functions as a tumor suppressor in breast cancer by negatively regulating cyclin E.International journal of oncology · 2026Article
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11 authors.
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Abstract
backgroundThe rising global incidence of metabolic syndrome (MetS) highlights the need for more effective diagnostic and therapeutic tools. Sphingolipid metabolites are crucial in MetS pathogenesis, and identifying related biomarkers could improve treatment strategies.
methodsDifferentially expressed genes (DEGs) were extracted from the GSE181646 dataset and compared with sphingolipid metabolism-related genes (SMRGs) to identify differentially expressed SMRGs (DE-SMRGs). Key module genes were obtained via Weighted Gene Co-expression Network Analysis (WGCNA). Machine learning and receiver operating characteristic (ROC) curve validation were used to screen biomarkers, followed by Gene Set Enrichment Analysis (GSEA) and immune cell infiltration analysis. Mendelian randomization (MR) was conducted to explore causal relationships between biomarkers and MetS-related diseases.
resultsA total of 701 DEGs, 599 key module genes, and 30 candidate genes were identified. PTPN18 and TAX1BP3 were validated as biomarkers and were found to be enriched in neuroactive ligand-receptor interactions and vascular smooth muscle contraction pathways. The levels of five immune cell types, including plasmacytoid dendritic cells, exhibited notable differences between the MetS and normal samples. TAX1BP3 exhibited a markedly negative correlation with activated CD8 T cell (r = -0.584), whereas it showed a markedly positive correlation with plasmacytoid dendritic cells (r = 0.744). MR analysis revealed that PTPN18 acted as a protective factor against obesity (P < 0.05, OR = 0.702), hyperlipidemia (P = 0.0015, OR = 0.855), and type 2 diabetes (P = 0.0026, OR = 0.953), but was associated with elevated fasting blood insulin (P < 0.05, OR = 1.036).
conclusionPTPN18 and TAX1BP3 were identified as sphingolipid metabolism-related biomarkers for MetS, offering potential promising targets for therapeutic intervention.
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