An novel effective and safe model for the diagnosis of nonalcoholic fatty liver disease in China: gene excavations, clinical validations, and mechanism elucidation

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. Due to the complexity and severity, an early diagnosis is crucial to guarantee a good quality of life. Methods The GSE89632 dataset was downloaded from the Gene Expression Omnibus database and then screened for differential genes using different machine learning methodologies. Blood samples from 320 NAFLD patients and livers from 12 mice were collected for experimental validation. Results AP-1 transcriptin factor subunit ( FOSB ), glycerol-3-phosphate acyltransferase 3 ( GPAT3 ), regulator of the cell cycle ( RGCC ), and ring finger protein 43 ( RNF43 ) were the key diagnostic genes for NAFLD, and they were further confirmed by a receiver operating characteristic curve analysis. we found that our selected genes when combined together, exhibited a strong ability in identifying NAFLD samples from normal samples (AUC = 0.997) and experimentally examined the expression of these genes in NAFLD patients and NAFLD mice with the same results. Conclusions Data from both clinical and animal studies demonstrate the high sensitivity, specificity and safety of FOSB, GPAT3, RGCC and RNF43 for the diagnosis of NAFLD. The relationship between diagnostic key genes and immune cell infiltration may help to understand the development of NAFLD. The study was reviewed and approved by Ethics Committee of Tianjin Second People's Hospital in 2021 (ChiCTR1900024415).