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探索ENPP5作为脓毒症的诊断生物标志物:一项全面的生物信息学分析

Exploring ENPP5 as a diagnostic biomarker for sepsis: a comprehensive bioinformatics analysis.

作者信息

Gao Jiamin, Li Yanjun, Huang Jinping, Wei Cailing, Chen Jieling, Huang Aichun, Liu Ningmei, Lu Yibo, Yang Shixiong

机构信息

Laboratory of Infectious Disease, HIV/AIDS Clinical Treatment Center of Guangxi (Nanning), The Fourth People's Hospital of Nanning, Nanning, 530023, China.

Department of Infectious Diseases, The Fourth People's Hospital of Nanning, Nanning, 530023, China.

出版信息

BMC Infect Dis. 2025 Jul 1;25(1):831. doi: 10.1186/s12879-025-11152-6.

Abstract

BACKGROUND

The rising mortality rates in sepsis highlight the current lack of reliable therapeutic biomarkers. This study aims to identify markers associated with biological functions to offer new strategies for sepsis diagnosis.

METHODS

We conducted differential expression analysis to identify differentially expressed messenger RNAs (DEmRs), long non-coding RNA (DElncRs), and microRNAs (DEmiRs) in sepsis compared to healthy controls. Enrichment analysis was performed using DEmRs, and a lncRNA-miRNA-mRNA competing endogenous RNA network was constructed. Least absolute shrinkage and selection operator (LASSO) and random forest models were applied to identify diagnostic mRNAs. The optimal diagnostic model was determined through decision curve analysis, resulting in the identification of seven hub genes. The key gene, determined by its highest importance and the largest area under the receiver operating characteristics curve (AUC) value, was further validated. Additionally, we analyzed the correlation of the key gene with microenvironment cell infiltration and immune genes.

RESULTS

A total of 4,450 intersected DEmRs (GSE66099, GSE13904, GSE154918, GSE8121) that were significantly involved in the cell cycle. We obtained 13 mRNAs, and further screened seven hub genes, including PPARD, ZSCAN2, ABI2, ENPP5, FMNL3, CD3E, and CAMK4. Subsequently, ENPP5 was as the key gene based on importance and AUC value. Moreover, Neutrophil cells and macrophages had a high abundance in sepsis patients. ENPP5 was positively associated with T cells but negatively associated with mast cells.

CONCLUSION

ENPP5, identified as a key gene, exhibits significant associations with immune cell infiltration and immune-related genes. This suggests its potential role as a biomarker for novel therapeutic strategies in sepsis.

摘要

背景

脓毒症死亡率的不断上升凸显了当前缺乏可靠的治疗生物标志物。本研究旨在识别与生物学功能相关的标志物,为脓毒症诊断提供新策略。

方法

我们进行了差异表达分析,以识别脓毒症患者与健康对照相比差异表达的信使核糖核酸(DEmRs)、长链非编码核糖核酸(DElncRs)和微小核糖核酸(DEmiRs)。使用DEmRs进行富集分析,并构建lncRNA-miRNA-mRNA竞争性内源RNA网络。应用最小绝对收缩和选择算子(LASSO)及随机森林模型识别诊断性mRNA。通过决策曲线分析确定最佳诊断模型,从而识别出7个枢纽基因。对重要性最高且受试者工作特征曲线(AUC)值最大的关键基因进行进一步验证。此外,我们分析了关键基因与微环境细胞浸润及免疫基因的相关性。

结果

共有4450个相交的DEmRs(GSE66099、GSE13904、GSE154918、GSE8121)显著参与细胞周期。我们获得了13个mRNA,并进一步筛选出7个枢纽基因,包括PPARD、ZSCAN2、ABI2、ENPP5、FMNL3、CD3E和CAMK4。随后,基于重要性和AUC值,ENPP5被确定为关键基因。此外,脓毒症患者中性粒细胞和巨噬细胞丰度较高。ENPP5与T细胞呈正相关,但与肥大细胞呈负相关。

结论

ENPP5被确定为关键基因,与免疫细胞浸润及免疫相关基因存在显著关联。这表明其在脓毒症新治疗策略中作为生物标志物的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2289/12211274/15576f343e56/12879_2025_11152_Fig1_HTML.jpg

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