脂质代谢相关基因标志物用于预测脓毒症患者生存状况的识别与验证
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1.西南医科大学;2.西南医科大学附属医院临床医学研究中心;3.西南医科大学临床医学院;4.泸州市人民医院

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泸州市医学会科研项目(2024-YXXM-111),泸州市医学会科研项目(2024-YXXM-040)


Identification and Validation of a Lipid Metabolism-associated Gene Signature for Predicting Survival in Sepsis Patients
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    摘要:

    目的:构建与脂质代谢相关的基因标志物,用于脓毒症患者的风险分层与免疫功能评估。方法:基于脓毒症数据集GSE65682,筛选脂质代谢相关基因。整合单因素Cox、LASSO与多因素Cox回归分析鉴定中心基因。根据风险评分中位数将患者分为高/低风险组。采用Kaplan-Meier与ROC曲线评估预测效能。通过ssGSEA、CIBERSORT算法与相关网络分析免疫功能差异。结果:筛选出包含AHRR、CLN8、FASN、LSS、MED29、PAFAH1B1、PIP5K1C、TRIB3、UGCG的9基因预后标志物。高风险组患者生存更差(KM检验p=6.75×e-8;ROC曲线下面积AUC=0.951),其趋化因子受体信号与副炎症反应富集。低风险组则显示出更高的肿瘤浸润淋巴细胞、II型干扰素应答、调节性T细胞与巨噬细胞浸润水平。免疫网络分析显示活化NK细胞与M1型巨噬细胞协同(r=0.44),与静息态NK细胞拮抗(r=-0.62)。CD86与TNFSF4在低风险组中高表达,而CD200R1被抑制。结论:基于脂质代谢的9基因标志物可有效预测脓毒症预后,揭示了高、低风险组间显著的免疫功能差异,为风险分层与个体化干预提供了潜在工具。

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    Objective: This study aimed to develop a lipid metabolism-associated gene signature to stratify sepsis patients for prognostic risk and evaluate their immune function.Methods: The sepsis dataset GSE65682 from GEO was used. Lipid metabolism-associated genes were identified via GeneCards and intersection analysis. Key genes were selected by integrating Univariate Cox, LASSO, and Multivariate Cox regression analyses. Patients were stratified into high- and low-risk groups based on the median risk score. Prognostic performance was validated using Kaplan-Meier analysis and Receiver Operating Characteristic (ROC) curves. Immune heterogeneity was assessed via single-sample Gene Set Enrichment Analysis (ssGSEA), the CIBERSORT algorithm, and correlation network analysis. Results: A 9-gene prognostic signature (AHRR, CLN8, FASN, LSS, MED29, PAFAH1B1, PIP5K1C, TRIB3, UGCG) demonstrated robust predictive performance. High-risk patients exhibited poorer survival (KM test, P=6.75 × e-8; ROC AUC: 0.951) and enrichment in chemokine receptor signaling and parainflammation. In contrast, low-risk patients showed higher infiltration levels of tumor-infiltrating lymphocytes, type II interferon response, regulatory T cells, and macrophages. Immune network analysis revealed coordinated interactions: activated NK cells synergized with M1 macrophages (r=0.44) but antagonized resting NK cells (r=-0.62). Immune checkpoints CD86 and TNFSF4 were upregulated in low-risk patients, while CD200R1 was suppressed.Conclusion: The established lipid metabolism-based 9-gene signature effectively predicts sepsis outcomes, revealing significant immune differences between risk groups. It provides a potential tool for risk stratification and personalized clinical intervention.

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  • 收稿日期:2026-03-09
  • 最后修改日期:2026-03-24
  • 录用日期:2026-04-09
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