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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R320.61

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四川省泸州市医学会科研项目(2024-YXXM-111);四川省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。此外,引入独立外部数据集 GSE95233进一 步验证模型的稳健性。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)为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的富集评分(P< 0.05)降低。模型在独立外部数据集 GSE95233的验证中,模型仍保持稳健的预测效能(AUC=0.757)。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。

    Abstract:

    Objective: To develop a lipid metabolism-associated gene signature to stratify sepsis patients for prognostic risk and evaluate their immune function. Methods: Based on the sepsis dataset GSE65682, lipid metabolism-related genes were screened. Univariate Cox regression, LASSO regression, and multivariate Cox regression analyses were integrated to identify hub genes. Patients were divided into high- and low-risk groups based on the median risk score. Kaplan-Meier and ROC curve analyses were used to evaluate predictive performance. Additionally, an independent external dataset, GSE95233, was introduced to further validate the robustness of the model. Immune function differences were analyzed using ssGSEA, CIBERSORT, and correlation network analysis. Results: A 9-gene prognostic signature was constructed, consisting of AHRR, CLN8, FASN, LSS, MED29, PAFAH1B1, PIP5K1C, TRIB3, and UGCG. Patients in the high-risk group showed poorer survival (KM test P=6.75×10??, area under the ROC curve AUC =0.951), with enrichment of chemokine receptor signaling and para-inflammatory responses. The low-risk group exhibited higher levels of tumor-infiltrating lymphocytes, type II interferon response, regulatory T cells, and macrophage infiltration. Immune network analysis revealed synergy between activated NK cells and M1 macrophages (r=0.44) and antagonism with resting NK cells (r=-0.62). CD86 and TNFSF4 were highly expressed in the low-risk group, while the enrichment score of CD200R1 was significantly reduced (P<0.05). The model maintained robust predictive performance in the independent external validation dataset GSE95233 (AUC=0.757). 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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薛珵馨;许欣欣;何思宇;余子寒;侯昊宇;游智茗;李其科;李勇.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[J].川北医学院学报,2026,41(6):652-654.

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  • 在线发布日期: 2026-06-12
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