Machine learning identifies ferroptosis-related gene ANXA2 as potential diagnostic biomarkers for NAFLD.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD), a major cause of chronic liver disease, still lacks effective therapeutic targets today. Ferroptosis, a type of cell death characterized by lipid peroxidation, has been linked to NAFLD in certain preclinical trials, yet the exact molecular mechanism remains unclear. Thus, we analyzed the relationship between ferroptosis genes and NAFLD using high-throughput data. METHOD: We utilized a total of 282 samples from five datasets, including two mouse ones, one human one, one single nucleus dataset and one single cell dataset from Gene Expression Omnibus (GEO), as the data basis of our study. To filter robust treatment targets, we employed four machine learning methods (LASSO, SVM, RF and Boruta). In addition, we used an unsupervised consensus clustering algorithm to establish a typing scheme for NAFLD based on the expression of ferroptosis related genes (FRGs). Our study is also the first to investigate the dynamics of FRGs throughout the disease process by time series analysis. Finally, we validated the relationship between core gene and ferroptosis by in vitro experiments on HepG2 cells. RESULTS: We discovered ANXA2 as a central focus in NAFLD and indicated its potential to boost ferroptosis in HepG2 cells. Additionally, based on the results obtained from time series analysis, ANXA2 was observed to significantly define the disease course of NAFLD. Our results demonstrate that implementing a ferroptosis-based staging method may hold promise for the diagnosis and treatment of NAFLD. CONCLUSION: Our findings suggest that ANXA2 may be a useful biomarker for the diagnosis and characterization of NAFLD.