Abstract

BackgroundThe prevalence of nonalcoholic fatty liver disease (NAFLD) is a major form of chronic liver disease. This study aimed to scrutinize the diagnostic biomarkers of NAFLD and their correlation with the immune microenvironment through bioinformatic analysis. MethodsTo identify genes associated with nonalcoholic fatty liver disease (NAFLD), we obtained microarray datasets (GSE63067 and GSE89632) from the Gene Expression Omnibus (GEO) database. Machine learning techniques such as Support Vector Machine (SVM), Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest (RF) were used to identify key genes. We performed gene ontology analysis to identify the driver pathways of NAFLD. External datasets (merging GSE48452, GSE66676 and GSE135251) were used to validate the identified genes and confirm protein levels by Western blotting. The CIBERSORT algorithm and immune-related techniques, such as ssGSEA, were used to assess the level of infiltration of different immune cell types and their functions. Finally, Spearman's analysis confirmed the relationship between pivotal genes and immune cells. ResultsHub genes (BBOX1, FOSB, NR4A2, RAB26 and SOCS2) were identified as potential biomarkers. This study demonstrates that these hub genes are significantly dysregulated in NAFLD, suggesting that they may be useful as diagnostic indicators and possible targets for treatment. Also covered are their possible effects on inflammation, immune cell activation, and liver damage in NAFLD. A better understanding of the intricate relationship between metabolic inefficiency, immunological response, and liver pathology in NAFLD may be gained from this work, which can lead to the development of new diagnostic tools and clinical treatments. ConclusionThe current study identified BBOX1, FOSB, NR4A2, RAB26 and SOCS2 as important diagnostic biomarkers for NAFLD. The study highlights the important function of immune cell infiltration in developing NAFLD. Their findings provide valuable molecular biological insights into the development of NAFLD and may lead to novel therapeutic strategies for treating this disease.

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