Ahnak and Nckap1l as potential diagnostic biomarkers and therapeutic targets in Landiolol-mediated sepsis treatment

IF 3.1 4区生物学 Q2 BIOLOGY

Computational Biology and Chemistry Pub Date : 2025-09-27 DOI:10.1016/j.compbiolchem.2025.108700

Weiyu Pan , Junli Cui , Su Tu , Bin Qian , Xiaoxia Liu , Xingping Zhu

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Abstract

Purpose

Landiolol is a beta-blocker used in the treatment of Sepsis. However, how this drug influences key genes and pathways involved in disease remains unknown. This study aimed to explore potential biomarkers involved in the mechanism of Landiolol’s action in sepsis.

Methods

Two microarray datasets from the Gene Expression Omnibus database were downloaded. Differentially expressed genes (DEGs) were identified. Then, Landiolol-associated genes (lnd-DEGs) were screened using weighted gene co-expression network analysis (WGCNA), followed by enrichment analysis and protein-protein interaction (PPI) network investigation. Biomarkers were explored using three machine learning methods (LASSO, SVM-RFE, and RF), followed by diagnostic and prognostic analyses of these biomarkers.

Results

After landiolol treatment, a total of 45 DEGs were identified when compared to normal samples. These genes were primarily associated with 357 biological functions, including the inositol phosphate metabolic process, and six key pathways, including the phosphatidylinositol signaling system. Using three different machine learning methods, 4 signature genes related to landiolol’s action on sepsis were identified. Receiver operating characteristic (ROC) analysis demonstrated high predictive accuracy for Ahnak and Nckap1l in sepsis. Clinical correlation analysis revealed that Nckap1l and Ahnak were significantly associated with endotype and overall survival (OS) of sepsis, respectively. Finally, the prognostic value of Ahnak was validated through Kaplan-Meier analysis.

Conclusions

Ahnak and Nckap1l are potential diagnostic biomarkers and targets for therapeutic intervention in landiolol-induced sepsis following administration of Landiolol. Nckap1l can be used for endotype analysis of sepsis.

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anhnak和nckap11在兰地洛尔介导的败血症治疗中的潜在诊断生物标志物和治疗靶点

目的盐酸地洛尔是一种用于治疗败血症的受体阻滞剂。然而，这种药物如何影响与疾病相关的关键基因和途径仍然未知。本研究旨在探索兰地洛尔在脓毒症中的作用机制的潜在生物标志物。方法从Gene Expression Omnibus数据库下载2个微阵列数据集。鉴定出差异表达基因（DEGs）。然后，通过加权基因共表达网络分析（WGCNA）筛选landiolol相关基因（lnd-DEGs），然后进行富集分析和蛋白-蛋白相互作用（PPI）网络研究。使用三种机器学习方法（LASSO、SVM-RFE和RF）探索生物标志物，然后对这些生物标志物进行诊断和预后分析。结果经兰地洛尔处理后，与正常样品相比，共鉴定出45个deg。这些基因主要与357个生物学功能相关，包括肌醇磷酸代谢过程和6个关键通路，包括磷脂酰肌醇信号系统。使用三种不同的机器学习方法，鉴定了4个与兰地洛尔对败血症作用相关的特征基因。受试者工作特征（ROC）分析显示Ahnak和nckap1在脓毒症中的预测准确度很高。临床相关分析显示，Nckap1l和Ahnak分别与脓毒症的endotype和overall survival （OS）显著相关。最后，通过Kaplan-Meier分析验证Ahnak的预后价值。结论sahnak和nckap1是兰地洛尔致脓毒症的潜在诊断生物标志物和治疗干预靶点。nckap11可用于脓毒症的内型分析。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Computational Biology and Chemistry 生物-计算机：跨学科应用

CiteScore

6.10

自引率

3.20%

发文量

142

审稿时长

24 days

期刊介绍： Computational Biology and Chemistry publishes original research papers and review articles in all areas of computational life sciences. High quality research contributions with a major computational component in the areas of nucleic acid and protein sequence research, molecular evolution, molecular genetics (functional genomics and proteomics), theory and practice of either biology-specific or chemical-biology-specific modeling, and structural biology of nucleic acids and proteins are particularly welcome. Exceptionally high quality research work in bioinformatics, systems biology, ecology, computational pharmacology, metabolism, biomedical engineering, epidemiology, and statistical genetics will also be considered. Given their inherent uncertainty, protein modeling and molecular docking studies should be thoroughly validated. In the absence of experimental results for validation, the use of molecular dynamics simulations along with detailed free energy calculations, for example, should be used as complementary techniques to support the major conclusions. Submissions of premature modeling exercises without additional biological insights will not be considered. Review articles will generally be commissioned by the editors and should not be submitted to the journal without explicit invitation. However prospective authors are welcome to send a brief (one to three pages) synopsis, which will be evaluated by the editors.