鉴定与非酒精性脂肪性肝病相关的代谢生物标志物。

Identification of metabolic biomarkers associated with nonalcoholic fatty liver disease.

机构信息

Department of Gastroenterology, The Affiffiffiliated YanAn Hospital of Kunming Medical University, Kunming, China.

出版信息

Lipids Health Dis. 2023 Sep 11;22(1):150. doi: 10.1186/s12944-023-01911-2.

BACKGROUND

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease. Metabolism-related genes significantly influence the onset and progression of the disease. Hence, it is necessary to screen metabolism-related biomarkers for the diagnosis and treatment of NAFLD patients.

METHODS

GSE48452, GSE63067, and GSE89632 datasets including nonalcoholic steatohepatitis (NASH) and healthy controls (HC) analyzed in this study were retrieved from the Gene Expression Omnibus (GEO) database. First, differentially expressed genes (DEGs) between NASH and HC samples were obtained. Next, metabolism-related DEGs (MR-DEGs) were identified by overlapping DEGs and metabolism-related genes (MRG). Further, a protein-protein interaction (PPI) network was developed to show the interaction among MR-DEGs. Subsequently, the "Least absolute shrinkage and selection operator regression" and "Random Forest" algorithms were used to screen metabolism-related genes (MRGs) in patients with NAFLD. Next, immune cell infiltration and gene set enrichment analyses (GSEA) were performed on these metabolism-related genes. Finally, the expression of metabolism-related gene was determined at the transcription level.

RESULTS

First, 129 DEGs related to NAFLD development were identified among patients with nonalcoholic steatohepatitis (NASH) and healthy control. Next, 18 MR-DEGs were identified using the Venn diagram. Subsequently, four genes, including AMDHD1, FMO1, LPL, and P4HA1, were identified using machine learning algorithms. Moreover, a regulatory network consisting of four genes, 25 microRNAs (miRNAs), and 41 transcription factors (TFs) was constructed. Finally, a significant increase in FMO1 and LPL expression levels and a decrease in AMDHD1 and P4HA1 expression levels were observed in patients in the NASH group compared to the HC group.

CONCLUSION

Metabolism-related genes associated with NAFLD were identified, containing AMDHD1, FMO1, LPL, and P4HA1, which provide insights into diagnosing and treating patients with NAFLD.

背景

非酒精性脂肪性肝病 (NAFLD) 是最常见的肝脏疾病。代谢相关基因对疾病的发生和发展有显著影响。因此，有必要筛选与代谢相关的生物标志物，用于诊断和治疗 NAFLD 患者。

方法

本研究从基因表达综合数据库 (GEO) 中检索了包括非酒精性脂肪性肝炎 (NASH) 和健康对照 (HC) 的 GSE48452、GSE63067 和 GSE89632 数据集。首先，获得 NASH 和 HC 样本之间的差异表达基因 (DEGs)。接下来，通过重叠 DEGs 和代谢相关基因 (MRG) 鉴定代谢相关 DEGs (MR-DEGs)。进一步构建蛋白质-蛋白质相互作用 (PPI) 网络，以显示 MR-DEGs 之间的相互作用。随后，采用“最小绝对收缩和选择算子回归”和“随机森林”算法筛选 NAFLD 患者的代谢相关基因 (MRGs)。接下来，对这些代谢相关基因进行免疫细胞浸润和基因集富集分析 (GSEA)。最后，在转录水平上测定代谢相关基因的表达。

结果

首先，在非酒精性脂肪性肝炎 (NASH) 患者和健康对照者中，鉴定出与 NAFLD 发生发展相关的 129 个 DEGs。接下来，使用 Venn 图鉴定出 18 个 MR-DEGs。随后，通过机器学习算法鉴定出 4 个基因，包括 AMDHD1、FMO1、LPL 和 P4HA1。此外，构建了一个由 4 个基因、25 个 microRNAs (miRNAs) 和 41 个转录因子 (TFs) 组成的调控网络。最后，与 HC 组相比，NASH 组患者的 FMO1 和 LPL 表达水平显著升高，AMDHD1 和 P4HA1 表达水平显著降低。