Identification of autophagy-related signatures in nonalcoholic fatty liver disease and correlation with non-parenchymal cells of the liver†

IF 3 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular omics Pub Date : 2024-07-10 DOI:10.1039/D4MO00060A

Kaiwei Chen, Ling Wei, Shengnan Yu, Ningning He and Fengjuan Zhang

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Abstract

Non-alcoholic fatty liver disease (NAFLD) is a chronic hepatic disease. The incidence and prevalence of NAFLD have increased greatly in recent years, and there is still a lack of effective drugs. Autophagy plays an important role in promoting liver metabolism and maintaining liver homeostasis, and defects in autophagy levels are considered to be related to the development of NAFLD. However, the molecular mechanisms of autophagy in NAFLD still remain unknown. In this study, we identified 6 autophagy-associated hub genes using gene expression profiles obtained from the GSE48452 and GSE89632 datasets. Biomarkers were screened according to gene significance (GS) and module membership (MM) using weighted gene co-expression network analysis (WGCNA), and the immune infiltration landscape of the liver in NAFLD patients was explored using the CIBERSORT algorithm. Subsequently, we analyzed the relationship between liver non-parenchymal cells and autophagy-related hub genes using scRNA-seq data (GSE129516). Finally, we separated the NAFLD patients into two groups based on 6 hub genes by consensus clustering and screened 10 potential autophagy-related small molecules based on the cMAP database.

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鉴定非酒精性脂肪肝中的自噬相关特征以及与非肝实质细胞的相关性。

非酒精性脂肪肝（NAFLD）是一种慢性肝病。近年来，非酒精性脂肪肝的发病率和患病率大幅上升，但目前仍缺乏有效的治疗药物。自噬在促进肝脏代谢和维持肝脏稳态方面发挥着重要作用，自噬水平的缺陷被认为与非酒精性脂肪肝的发生有关。然而，自噬在非酒精性脂肪肝中的分子机制仍然未知。在本研究中，我们利用从 GSE48452 和 GSE89632 数据集中获得的基因表达谱鉴定了 6 个与自噬相关的枢纽基因。利用加权基因共表达网络分析（WGCNA）根据基因的显著性（GS）和模块成员性（MM）筛选生物标志物，并利用 CIBERSORT 算法探索非酒精性脂肪肝患者肝脏的免疫浸润情况。随后，我们利用 scRNA-seq 数据（GSE129516）分析了肝脏非实质性细胞与自噬相关枢纽基因之间的关系。最后，我们通过共识聚类将非酒精性脂肪肝患者根据 6 个中心基因分为两组，并根据 cMAP 数据库筛选出 10 个潜在的自噬相关小分子。

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来源期刊

Molecular omics Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

5.40

自引率

3.40%

发文量

期刊介绍： Molecular Omics publishes high-quality research from across the -omics sciences. Topics include, but are not limited to: -omics studies to gain mechanistic insight into biological processes – for example, determining the mode of action of a drug or the basis of a particular phenotype, such as drought tolerance -omics studies for clinical applications with validation, such as finding biomarkers for diagnostics or potential new drug targets -omics studies looking at the sub-cellular make-up of cells – for example, the subcellular localisation of certain proteins or post-translational modifications or new imaging techniques -studies presenting new methods and tools to support omics studies, including new spectroscopic/chromatographic techniques, chip-based/array technologies and new classification/data analysis techniques. New methods should be proven and demonstrate an advance in the field. Molecular Omics only accepts articles of high importance and interest that provide significant new insight into important chemical or biological problems. This could be fundamental research that significantly increases understanding or research that demonstrates clear functional benefits. Papers reporting new results that could be routinely predicted, do not show a significant improvement over known research, or are of interest only to the specialist in the area are not suitable for publication in Molecular Omics.