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机器学习和转录组分析可识别慢性肾病患者的肾小管损伤生物标志物。

Machine learning and transcriptomic analysis identify tubular injury biomarkers in patients with chronic kidney disease.

作者信息

Sun Feifei, Cai Jiahui, Pan Qiaoyun, Sun Yunbo, Zhao Shasha, Liu Weiping, Tan Qiang, Yan Yanling

机构信息

Key Labs Nanobiotech and Applied Chemistry, Department of Biotechnology and Engineering, College of Environmental and Chemistry Engineering, Yanshan University, Qinhuangdao, 066004, China.

Divisions of Nephrology and Cardiology, The First Hospital of Qinhuangdao, Qinhuangdao, China.

出版信息

Int Urol Nephrol. 2025 Jun 30. doi: 10.1007/s11255-025-04636-6.

Abstract

PURPOSE

Chronic Kidney Disease (CKD) is emerging as a major public health problem, with a lack of precise diagnostic biomarkers in clinical settings. The primary objective is to discover biomarkers for early clinical detection of CKD and to gain a deeper understanding of its underlying pathophysiological processes.

METHODS

Samples from renal tubules of CKD patients and healthy controls were subjected to differential expression analysis. Weighted Gene Co-expression Network Analysis (WGCNA) was utilized to detect genes associated with renal tubular damage in CKD. Subsequently, Support Vector Machine Recursive Feature Elimination (SVM-RFE) and Least Absolute Shrinkage and Selection Operator (LASSO) algorithms were employed to identify and validate potential biomarker candidates.

RESULTS

Four key renal biomarkers, namely DUSP1, GADD45A, TSC22D3, and ZFAND5, were successfully identified. Receiver Operating Characteristic (ROC) curve analysis and nomogram construction demonstrated their remarkable diagnostic capabilities. These biomarkers were also found to affect the degree of immune cell infiltration in CKD and exhibited a notable correlation with Glomerular Filtration Rate (GFR) and serum creatinine (SCr) levels.

CONCLUSION

These four identified biomarkers for renal tubular injury play important roles in immune function and inflammatory responses in CKD, potentially providing a theoretical foundation for dissecting molecular mechanisms and developing therapeutic strategies in CKD.

摘要

目的

慢性肾脏病(CKD)正成为一个主要的公共卫生问题,临床环境中缺乏精确的诊断生物标志物。主要目标是发现用于CKD早期临床检测的生物标志物,并更深入地了解其潜在的病理生理过程。

方法

对CKD患者和健康对照的肾小管样本进行差异表达分析。利用加权基因共表达网络分析(WGCNA)检测与CKD肾小管损伤相关的基因。随后,采用支持向量机递归特征消除(SVM-RFE)和最小绝对收缩和选择算子(LASSO)算法来识别和验证潜在的生物标志物候选物。

结果

成功鉴定出四种关键的肾脏生物标志物,即双特异性磷酸酶1(DUSP1)、生长停滞和DNA损伤诱导蛋白45α(GADD45A)、TSC22结构域蛋白3(TSC22D3)和锌指抗病毒蛋白5(ZFAND5)。受试者工作特征(ROC)曲线分析和列线图构建证明了它们卓越的诊断能力。还发现这些生物标志物会影响CKD中免疫细胞浸润的程度,并且与肾小球滤过率(GFR)和血清肌酐(SCr)水平呈现出显著相关性。

结论

这四种鉴定出的肾小管损伤生物标志物在CKD的免疫功能和炎症反应中发挥重要作用,可能为剖析CKD的分子机制和制定治疗策略提供理论基础。

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