基于生物信息学分析和机器学习的非酒精性脂肪性肝病（NAFLD）合并慢性肾脏病（CKD）诊断生物标志物的鉴定。
Identification of biomarkers for the diagnosis of chronic kidney disease (CKD) with non-alcoholic fatty liver disease (NAFLD) by bioinformatics analysis and machine learning.
机构信息
Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
Department of Nephrology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
出版信息
Front Endocrinol (Lausanne). 2023 Feb 27;14:1125829. doi: 10.3389/fendo.2023.1125829. eCollection 2023.
BACKGROUND
Chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) are closely related to immune and inflammatory pathways. This study aimed to explore the diagnostic markers for CKD patients with NAFLD.
METHODS
CKD and NAFLD microarray data sets were screened from the GEO database and analyzed the differentially expressed genes (DEGs) in GSE10495 of CKD date set. Weighted Gene Co-Expression Network Analysis (WGCNA) method was used to construct gene coexpression networks and identify functional modules of NAFLD in GSE89632 date set. Then obtaining NAFLD-related share genes by intersecting DEGs of CKD and modular genes of NAFLD. Then functional enrichment analysis of NAFLD-related share genes was performed. The NAFLD-related hub genes come from intersection of cytoscape software and machine learning. ROC curves were used to examine the diagnostic value of NAFLD related hub genes in the CKD data sets and GSE89632 date set of NAFLD. CIBERSORTx was also used to explore the immune landscape in GSE104954, and the correlation between immune infiltration and hub genes expression was investigated.
RESULTS
A total of 45 NAFLD-related share genes were obtained, and 4 were NAFLD-related hub genes. Enrichment analysis showed that the NAFLD-related share genes were significantly enriched in immune-related pathways, programmed cell death, and inflammatory response. ROC curve confirmed 4 NAFLD-related hub genes in CKD training set GSE104954 and other validation sets. Then they were used as diagnostic markers for CKD. Interestingly, these 4 diagnostic markers of CKD also showed good diagnostic value in the NAFLD date set GSE89632, so these genes may be important targets of NAFLD in the development of CKD. The expression levels of the 4 diagnostic markers for CKD were significantly correlated with the infiltration of immune cells.
CONCLUSION
4 NAFLD-related genes (DUSP1, NR4A1, FOSB, ZFP36) were identified as diagnostic markers in CKD patients with NAFLD. Our study may provide diagnostic markers and therapeutic targets for CKD patients with NAFLD.
背景
慢性肾脏病（CKD）和非酒精性脂肪性肝病（NAFLD）与免疫和炎症途径密切相关。本研究旨在探讨伴有 NAFLD 的 CKD 患者的诊断标志物。
方法
从 GEO 数据库中筛选出 CKD 和 NAFLD 的微阵列数据集，并分析 GSE10495 中 CKD 数据集的差异表达基因（DEGs）。使用加权基因共表达网络分析（WGCNA）方法构建基因共表达网络，并识别 GSE89632 数据集的 NAFLD 功能模块。然后通过将 CKD 的 DEGs 和 NAFLD 的模块基因相交，获得与 NAFLD 相关的共享基因。然后对与 NAFLD 相关的共享基因进行功能富集分析。NAFLD 相关的枢纽基因来自于 Cytoscape 软件和机器学习的交集。ROC 曲线用于检验 CKD 数据集中与 NAFLD 相关的枢纽基因的诊断价值以及 GSE89632 数据集的 NAFLD。还使用 CIBERSORTx 探索 GSE104954 中的免疫景观，并研究免疫浸润与枢纽基因表达之间的相关性。
结果
共获得 45 个与 NAFLD 相关的共享基因，其中 4 个是与 NAFLD 相关的枢纽基因。富集分析表明，与 NAFLD 相关的共享基因在免疫相关途径、程序性细胞死亡和炎症反应中显著富集。ROC 曲线证实了 CKD 训练集 GSE104954 中的 4 个与 NAFLD 相关的枢纽基因和其他验证集。然后，它们被用作 CKD 的诊断标志物。有趣的是，这些 4 个 CKD 的诊断标志物在 GSE89632 数据集的 NAFLD 中也表现出良好的诊断价值，因此这些基因可能是 NAFLD 导致 CKD 发展的重要靶点。这 4 个 CKD 诊断标志物的表达水平与免疫细胞的浸润显著相关。
结论
鉴定出 4 个与 NAFLD 相关的基因（DUSP1、NR4A1、FOSB、ZFP36）作为伴有 NAFLD 的 CKD 患者的诊断标志物。我们的研究可能为伴有 NAFLD 的 CKD 患者提供诊断标志物和治疗靶点。
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