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<p>Pneumonia-induced sepsis (PIS) is a life-threatening condition with high mortality rates, necessitating the identification of biomarkers and therapeutic targets. Sphingolipid, particularly ceramides, are pivotal in modulating immune responses and determining cell fate. In this study, we identified a novel gene signature related to sphingolipid metabolism, comprising <i>ACER3</i>, <i>UGCG</i>, and <i>GBA</i>, which are key enzymes involved in the synthesis and metabolism of ceramides. This signature, termed the “AUG model”, demonstrated strong diagnostic performance and modest prognostic efficacy across both training (GSE65682) and validation (E-MTAB-1548 and E-MTAB-5273) datasets. A clinical cohort comprising 20 PIS patients, 31 pneumonia cases, and 11 healthy controls further validated the increased expression of AUG genes at both mRNA and protein levels in peripheral blood samples upon admission. Our comprehensive analysis of bulk and single-cell transcriptome datasets revealed that these genes are implicated in immune cell death pathways, including autophagy and apoptosis. Additionally, cell-communication analysis indicated that enhanced macrophage migration inhibitory factor (MIF) signaling may be associated with dysregulated sphingolipid metabolism, potentially driving the inflammatory cascade. This study identifies a novel predictive model for PIS, highlighting the role of sphingolipid metabolism-related genes in disease progression and suggesting potential therapeutic targets for sepsis management.</p>

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Sphingolipid metabolism-related genes as diagnostic markers in pneumonia-induced sepsis: the AUG model

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月20日

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  • Jing Wu,
  • Xiaomin Li,
  • Zhihao Chen,
  • Yiting Lin,
  • Qiuyue Long,
  • Mingzheng Jiang,
  • Xiaoyi Hu,
  • Shixu Song,
  • Hongli Ye,
  • Jiwei Li,
  • Fangfang Wu,
  • Jianshi Zheng,
  • Minghui Wang,
  • Zhancheng Gao,
  • Pu Ning,
  • Yali Zheng

摘要

Pneumonia-induced sepsis (PIS) is a life-threatening condition with high mortality rates, necessitating the identification of biomarkers and therapeutic targets. Sphingolipid, particularly ceramides, are pivotal in modulating immune responses and determining cell fate. In this study, we identified a novel gene signature related to sphingolipid metabolism, comprising ACER3, UGCG, and GBA, which are key enzymes involved in the synthesis and metabolism of ceramides. This signature, termed the “AUG model”, demonstrated strong diagnostic performance and modest prognostic efficacy across both training (GSE65682) and validation (E-MTAB-1548 and E-MTAB-5273) datasets. A clinical cohort comprising 20 PIS patients, 31 pneumonia cases, and 11 healthy controls further validated the increased expression of AUG genes at both mRNA and protein levels in peripheral blood samples upon admission. Our comprehensive analysis of bulk and single-cell transcriptome datasets revealed that these genes are implicated in immune cell death pathways, including autophagy and apoptosis. Additionally, cell-communication analysis indicated that enhanced macrophage migration inhibitory factor (MIF) signaling may be associated with dysregulated sphingolipid metabolism, potentially driving the inflammatory cascade. This study identifies a novel predictive model for PIS, highlighting the role of sphingolipid metabolism-related genes in disease progression and suggesting potential therapeutic targets for sepsis management.