Identification of Biomarkers and Immune-Metabolic Regulators in Acute Pancreatitis and Sarcopenia: A Multi-Modal Transcriptomics Study.

Studies suggest a clinically significant association between acute pancreatitis and sarcopenia. However, the molecular mechanisms behind this association have not been fully elucidated. Here, we systematically investigated gene expression profiles by differentially expressed gene (DEG) analysis, weighted gene co-expression network analysis (WGCNA) and functional enrichment analysis, and identified a total of 36 genes as shared genes between acute pancreatitis and sarcopenia. Functional enrichment analysis revealed that these genes were enriched in immune-inflammatory processes and pathways. Furthermore, we evaluated relevant hub genes in a random forest model and investigated their expression, diagnostic performance and immune cell relationships. Random forest modelling prioritised chloride intracellular channel 5 (CLIC5), solute carrier family 38 member 1 (SLC38A1) and complement C1q B chain (C1QB) as key candidate biomarkers. Immune infiltration analysis linked these genes to dysregulated T cells, monocytes and mast cells in both diseases. Finally, we constructed a regulatory network involving miRNAs, mRNAs and transcription factors to illustrate further the regulations of three genes' transcription in acute pancreatitis and sarcopenia. The diagnostic value of CLIC5, SLC38A1 and C1QB was performed by receiver operating characteristic curves and the area under the curve in the datasets, and the validation results confirmed a consistent trend of downregulation of CLIC5 and SLC38A1 in AP and sarcopenia. This study revealed for the first time that CLIC5 and SLC38A1 were shared biomarkers for AP and sarcopenia. Their association with immune-metabolic dysregulation highlights their potential as therapeutic targets.