Identification and validation of disulfidptosis-associated molecular clusters in non-alcoholic fatty liver disease

作者：Xiaoxiao Yu, Zihao Guo, Zhihao Fang, Kai Yang, Changxu Liu, Zhichao Dong, Chang Liu · 发表于：Frontiers in Genetics · 年份：2023 · DOI：10.3389/fgene.2023.1251999 · 被引用次数：21 · 研究领域：Liver Disease Diagnosis and Treatment、Endoplasmic Reticulum Stress and Disease、Cancer-related molecular mechanisms research

Objective: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the world, and its pathogenesis is not fully understood. Disulfidptosis is the most recently reported form of cell death and may be associated with NAFLD progression. Our study aimed to explore the molecular clusters associated with disulfidptosis in NAFLD and to construct a predictive model. Methods: First, we analyzed the expression profile of the disulfidptosis regulators and immune characteristics in NAFLD. Using 104 NAFLD samples, we investigated molecular clusters based on differentially expressed disulfidptosis-related genes, along with the related immune cell infiltration. Cluster-specific differentially expressed genes were then identified by using the WGCNA method. We also evaluated the performance of four machine learning models before choosing the optimal machine model for diagnosis. Nomogram, calibration curves, decision curve analysis, and external datasets were used to confirm the prediction effectiveness. Finally, the expression levels of the biomarkers were assessed in a mouse model of a high-fat diet. Results: Two differentially expressed DRGs were identified between healthy and NAFLD patients. We revealed the expression profile of DRGs in NAFLD and the correlation with 22 immune cells. In NAFLD, two clusters of molecules connected to disulfidptosis were defined. Significant immunological heterogeneity was shown by immune infiltration analysis among the various cluste...