LCN2 and TIMP1 as senescence-associated biomarkers in sepsis-induced AKI and their relationship with immune infiltration.

IF 2.1 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Biomarkers in medicine Pub Date : 2026-04-01 Epub Date: 2026-06-01 DOI:10.1080/17520363.2026.2671010

Aijing Huo, Xue Yang

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引用次数: 0

Abstract

Background: Immune cells are key drivers of acute kidney injury (AKI) due to the complex interaction between immune cells, senescence and AKI.

Material and methods: Three AKI-related datasets were sourced from the Gene Expression Omnibus (GEO) database, encompassing experimental data and gene expression arrays. TIMP1 and LCN2 were used to construct the AKI diagnostic model, and the resulting nomogram and Receiver Operating Characteristic (ROC) curves exhibited significant diagnostic efficacy. Within the framework of AKI patients, the increased protein expression of LCN2 and TIMP1 was corroborated through Enzyme-Linked Immunosorbent Assay (ELISA).

Results: The precision of the risk predictive model's classification based on signature ARGs, was validated by ROC curves, with an area under the curve (AUC) of 0.9596 in the training cohort; the optimized LCN2/TIMP1 dual-gene diagnostic model showed an AUC of 0.997 in the training set. Utilizing the CIBERSORT algorithm, it was observed that sepsis-induced AKI models exhibited elevated levels of Macrophages M1, T cells follicular helper and so on, and sepsis-induced AKI models had lower levels of dendritic cells resting.

Conclusions: The management of AKI emphasizes the senescence-association of LCN2 and TIMP1 genes with immune cells. As a pilot study with a small sample size, more prospective approaches could be considered to demonstrate this argument.

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LCN2和TIMP1在败血症诱导的AKI中作为衰老相关的生物标志物及其与免疫浸润的关系

背景：由于免疫细胞、衰老和AKI之间复杂的相互作用，免疫细胞是急性肾损伤（AKI）的关键驱动因素。材料和方法：三个与aki相关的数据集来自Gene Expression Omnibus （GEO）数据库，包括实验数据和基因表达阵列。采用TIMP1和LCN2构建AKI诊断模型，得到的nomogram和Receiver Operating Characteristic （ROC）曲线具有显著的诊断效果。在AKI患者的框架内，通过酶联免疫吸附试验（ELISA）证实了LCN2和TIMP1蛋白表达的增加。结果：ROC曲线验证了基于特征ARGs的风险预测模型分类的准确性，训练队列的曲线下面积（AUC）为0.9596；优化后的LCN2/TIMP1双基因诊断模型在训练集中的AUC为0.997。利用CIBERSORT算法，我们观察到败血症诱导的AKI模型中巨噬细胞M1、T细胞滤泡辅助细胞等水平升高，而败血症诱导的AKI模型中树突状细胞静息水平降低。结论：AKI的治疗强调LCN2和TIMP1基因与免疫细胞的衰老关联。作为一个小样本量的试点研究，可以考虑更多的前瞻性方法来证明这一论点。

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

Biomarkers in medicine 医学-医学：研究与实验

CiteScore

3.80

自引率

4.50%

发文量

审稿时长

6-12 weeks

期刊介绍： Biomarkers are physical, functional or biochemical indicators of physiological or disease processes. These key indicators can provide vital information in determining disease prognosis, in predicting of response to therapies, adverse events and drug interactions, and in establishing baseline risk. The explosion of interest in biomarker research is driving the development of new predictive, diagnostic and prognostic products in modern medical practice, and biomarkers are also playing an increasingly important role in the discovery and development of new drugs. For the full utility of biomarkers to be realized, we require greater understanding of disease mechanisms, and the interplay between disease mechanisms, therapeutic interventions and the proposed biomarkers. However, in attempting to evaluate the pros and cons of biomarkers systematically, we are moving into new, challenging territory. Biomarkers in Medicine (ISSN 1752-0363) is a peer-reviewed, rapid publication journal delivering commentary and analysis on the advances in our understanding of biomarkers and their potential and actual applications in medicine. The journal facilitates translation of our research knowledge into the clinic to increase the effectiveness of medical practice. As the scientific rationale and regulatory acceptance for biomarkers in medicine and in drug development become more fully established, Biomarkers in Medicine provides the platform for all players in this increasingly vital area to communicate and debate all issues relating to the potential utility and applications. Each issue includes a diversity of content to provide rounded coverage for the research professional. Articles include Guest Editorials, Interviews, Reviews, Research Articles, Perspectives, Priority Paper Evaluations, Special Reports, Case Reports, Conference Reports and Company Profiles. Review coverage is divided into themed sections according to area of therapeutic utility with some issues including themed sections on an area of topical interest. Biomarkers in Medicine provides a platform for commentary and debate for all professionals with an interest in the identification of biomarkers, elucidation of their role and formalization and approval of their application in modern medicine. The audience for Biomarkers in Medicine includes academic and industrial researchers, clinicians, pathologists, clinical chemists and regulatory professionals.