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Background <p>Apoptosis occupies a core position in the pathogenesis of multiple organ dysfunction syndrome (MODS). Therefore, exploring key mechanisms of action of apoptosis-related genes (ARGs) in MODS will play a positive and promoting role in the diagnosis and treatment of MODS.</p> Methods <p>We obtained MODS-related data from public databases, and analyzed the disparately expressed genes between MODS and controls, as well as the weighted gene co-expression network analysis (WGCNA) genes most related to MODS. The intersection with ARGs was then used to obtain candidate genes. After that, by combining Cytoscape software, machine learning algorithms with expression verification, key genes were obtained, and a nomogram model was constructed and evaluated. Next, centering on key genes, gene set enrichment analysis, immune infiltration analysis, small ubiquitin-like modifier (SUMO) analysis, regulatory network construction, and drug prediction were carried out. At last, the expression of key genes in clinical samples was validated.</p> Results <p>After screening, S100A9, S100A8, and BCL2A1 were identified as the key genes of MODS. They were all significantly highly expressed in MODS and jointly participated in "oxidative phosphorylation" signaling pathway. The nomogram constructed based on the key genes had excellent predictive ability. There were 15 types of differentially infiltrated immune cells between MODS and controls, and they were correlated with the key genes. In addition, each of the key genes had two or more SUMOylation sites, and multiple miRNAs (hsa-let-7d-5p) and lncRNAs (XIST) were predicted. Subsequently, the key genes also jointly predicted potential drugs (curcumin). Finally, in clinical samples of MODS, the key genes also showed high expression.</p> Conclusion <p>S100A9, S100A8, and BCL2A1 were the key genes of MODS in terms of apoptosis. The constructed nomogram had an excellent predictive value. It offers a novel approach and potential targeted therapy for the clinical diagnosis and treatment of MODS.</p>

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Identification and validation of key genes related to apoptosis in multiple organ dysfunction syndrome

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月7日

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  • Jian Zhang,
  • Zhi-ying Wen,
  • Yan-xiao Li,
  • Hui-ping Sun,
  • ying-ying Zheng

摘要

Background

Apoptosis occupies a core position in the pathogenesis of multiple organ dysfunction syndrome (MODS). Therefore, exploring key mechanisms of action of apoptosis-related genes (ARGs) in MODS will play a positive and promoting role in the diagnosis and treatment of MODS.

Methods

We obtained MODS-related data from public databases, and analyzed the disparately expressed genes between MODS and controls, as well as the weighted gene co-expression network analysis (WGCNA) genes most related to MODS. The intersection with ARGs was then used to obtain candidate genes. After that, by combining Cytoscape software, machine learning algorithms with expression verification, key genes were obtained, and a nomogram model was constructed and evaluated. Next, centering on key genes, gene set enrichment analysis, immune infiltration analysis, small ubiquitin-like modifier (SUMO) analysis, regulatory network construction, and drug prediction were carried out. At last, the expression of key genes in clinical samples was validated.

Results

After screening, S100A9, S100A8, and BCL2A1 were identified as the key genes of MODS. They were all significantly highly expressed in MODS and jointly participated in "oxidative phosphorylation" signaling pathway. The nomogram constructed based on the key genes had excellent predictive ability. There were 15 types of differentially infiltrated immune cells between MODS and controls, and they were correlated with the key genes. In addition, each of the key genes had two or more SUMOylation sites, and multiple miRNAs (hsa-let-7d-5p) and lncRNAs (XIST) were predicted. Subsequently, the key genes also jointly predicted potential drugs (curcumin). Finally, in clinical samples of MODS, the key genes also showed high expression.

Conclusion

S100A9, S100A8, and BCL2A1 were the key genes of MODS in terms of apoptosis. The constructed nomogram had an excellent predictive value. It offers a novel approach and potential targeted therapy for the clinical diagnosis and treatment of MODS.