Zhang Jian, Wang Huiwen, Wang Qianbing, Mo Juan, Fu Lei, Peng Shifang
Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Infection Control Center of Xiangya Hospital, Central South University, Changsha, Hunan, China.
Mamm Genome. 2025 Mar;36(1):93-105. doi: 10.1007/s00335-024-10078-9. Epub 2024 Oct 16.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disease that ranges from metabolic dysfunction-associated steatotic liver (MASL) to metabolic dysfunction-associated steatohepatitis (MASH), and may eventually progress to cirrhosis and hepatocellular carcinoma (HCC). The underlying mechanism of MASLD remains incompletely understood. This study aimed to identify key gene implicated in MASLD pathogenesis and validate its correlation with disease severity through an integration of bioinformatics and experimental approaches. Liver transcriptome data from MASLD patients were obtained from the Gene Expression Omnibus (GEO) database. A diet-induced MASLD mouse model was developed, and liver RNA-sequencing was performed. Liver specimens and clinical data from patients were collected for further analysis. A total of 120 differentially expressed genes (DEGs) were shared between datasets GSE89632 and GSE213621, with functional enrichment in inflammatory, metabolic, and cell cycle-related pathways. Protein-protein interaction (PPI) network analysis identified three modules associated with MASLD, with the cell cycle-related module being the most notable. EEF1A2 was identified as a novel hub gene and revealed to be elevated with MASLD progression through dataset analysis. EEF1A2 was confirmed to be highly expressed in the livers of both MASLD mouse models and patients. Moreover, the increased expression of EEF1A2 in MASH was positively correlated with higher serum alanine aminotransferase (ALT), alanine aminotransferase (AST), total cholesterol (TC), and body mass index (BMI). In conclusion, EEF1A2 is a novel hub gene significantly associated with MASLD severity and is a promising biomarker and therapeutic target for MASLD.
代谢功能障碍相关脂肪性肝病（MASLD）是一种常见的慢性肝病，范围从代谢功能障碍相关脂肪性肝病（MASL）到代谢功能障碍相关脂肪性肝炎（MASH），并可能最终进展为肝硬化和肝细胞癌（HCC）。MASLD的潜在机制仍未完全了解。本研究旨在通过整合生物信息学和实验方法，鉴定参与MASLD发病机制的关键基因，并验证其与疾病严重程度的相关性。从基因表达综合数据库（GEO）中获取MASLD患者的肝脏转录组数据。建立饮食诱导的MASLD小鼠模型，并进行肝脏RNA测序。收集患者的肝脏标本和临床数据进行进一步分析。数据集GSE89632和GSE213621共有120个差异表达基因（DEG），在炎症、代谢和细胞周期相关途径中功能富集。蛋白质-蛋白质相互作用（PPI）网络分析确定了与MASLD相关的三个模块，其中细胞周期相关模块最为显著。通过数据集分析，EEF1A2被鉴定为一个新的中心基因，并显示其随着MASLD进展而升高。EEF1A2在MASLD小鼠模型和患者的肝脏中均被证实高表达。此外，MASH中EEF1A2表达的增加与较高的血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆固醇（TC）和体重指数（BMI）呈正相关。总之，EEF1A2是一个与MASLD严重程度显著相关的新中心基因，是MASLD有前景的生物标志物和治疗靶点。
