Comprehensive Analysis Reveals the Molecular Features and Immune Infiltration of PANoptosis-Related Genes in Metabolic Dysfunction-Associated Steatotic Liver Disease

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  Figure 3. Identification of the key differentially expressed genes associated with PANoptosis (PANoDEGs) in nonalcoholic liver disease. (A) The protein–protein interaction network signature. (B,C) The Least Absolute Shrinkage and Selection Operator (LASSO) algorithm filtered the PANoDEGs. (D) PANoDEGs were prioritized through the SVM-RFE algorithm. (E) Venn diagram of critical PANoDEGs by LASSO and SVM-RFE. The shared selection of PANoDEGs by LASSO and SVM-RFE in the Venn diagram is designated as the key PANoDEGs.

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  Figure 4. Diagnostic effect of key differentially expressed genes associated with PANoptosis (PANoDEGs), gene set enrichment analysis of key PANoDEGs, and immune infiltration. (A–D) Receiver operating characteristic (ROC) curves for assessing the diagnostic validity of critical PANoDEGs using the GSE126848 dataset. (E–H) ROC curves for the diagnostic validity of critical PANoDEGs evaluated using the GSE135251 dataset. (I–K) The five pathways with the highest enrichment scores including SNHG16, Caspase-6 (CASP6), and DNM1L. (L) Comparison of immune cell subtypes in nonalcoholic fatty liver disease and control liver, blue represents the control group, and red represents the disease group.

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  Figure 5. The immune infiltration analysis and network analysis of key differentially expressed genes associated with PANoptosis (PANoDEGs). (A) Correlation between SNHG16 and immune cells. (B) Correlation between CASP6 and immune cells. (C) Correlation between DNM1L and immune cells. (D) Key PANoDEGs–drug network analysis based on the CTD database. (E) Regulatory network of transcription factors and key PANoDEGs. (F) Microribonucleic acid and key PANoDEGs regulatory networks.

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  Figure 1. The key flowchart of this study. * p < 0.05, ** p < 0.01, *** p < 0.001.

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  Figure 2. Identification of differentially expressed genes associated with PANoptosis (PANoDEGs) in nonalcoholic fatty liver disease and functional enrichment analysis. (A,B) Volcano plot and heatmap of DEGs in GSE126848. (C) Venn plots of the genes associated with DEGs and PANoptosis-related genes. (D) Heatmap of PANoDEGs in the GSE126848 dataset. (E) Heatmap of the correlation among the PANoDEGs genes. (F) Gene Ontology enrichment analysis of PANoDEGs, biological process, cellular component, and molecular function. (G) Kyoto Encyclopedia of Genes and Genomes pathway enrichment for PANoDEGs. * p < 0.05, *** p < 0.001.

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  Figure 6. Validation of the expression of key differentially expressed genes associated with PANoptosis (PANoDEGs) in MASLD mouse models and cells. (A) Hematoxylin–eosin and Oil Red O staining of the control and MASLD livers of mice; bar (4×) = 200 μm and bar (20×) = 50 μm. (B) The relative values of ALT and AST in mouse serum. (C–E) Reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis of key PANoDEGs messenger ribonucleic acid (mRNA) levels in the control and MASLD livers of mice. (F,G) RT-qPCR analysis of key PANoDEGs mRNA levels of the control and PA-treated cells. (H–J) Results of the RT-qPCR analysis performed to measure the mRNA levels of key PANoDEGs in the blood samples obtained from the control group and MASLD group. * p < 0.05, ** p < 0.01, *** p < 0.001.