Long non-coding RNA AC245100.4 for early diagnosis and prognostic assessment in acute pancreatitis: clinical value and inflammation-regulatory mechanisms

Objective To determine whether serum exosomal long non-coding RNA AC245100.4 has value for early diagnosis and prognostic stratification in acute pancreatitis (AP), and to examine its potential involvement in inflammation-related cellular communication. Methods A total of 228 participants were enrolled during the early admission phase, including 152 patients with AP and 76 controls with non-pancreatic acute abdominal diseases. Serum samples were collected within the predefined early window (T0, within 24 h of admission and within 48 h of symptom onset). Exosomes were isolated and characterized by transmission electron microscopy, nanoparticle tracking analysis, and exosomal protein marker validation. Exosomal AC245100.4 expression was measured by quantitative reverse-transcription polymerase chain reaction. Its diagnostic and prognostic associations with severe acute pancreatitis (SAP) and persistent organ failure (OF) were evaluated, including its additive value beyond established clinical scoring systems. Candidate downstream regulatory pathways were prioritized through bioinformatic screening and further examined using an acinar cell–macrophage co-culture model and targeted molecular assays. Results Exosomal AC245100.4 was significantly elevated in patients with AP compared with controls and showed further stepwise increases in patients with SAP and persistent OF. It demonstrated good discriminatory performance for early diagnosis and early risk stratification, with AUCs ranging from 0.84 to 0.88, and improved model discrimination when incorporated into existing clinical assessment frameworks. Mechanistic analyses suggested that AC245100.4 may contribute to inflammatory crosstalk between acinar cells and macrophages. Integrated molecular evidence supported partial involvement of an AC245100.4/miR-146a-5p/NLRP3-related regulatory pathway, together with enhanced nuclear factor kappa B activation and inflammasome-associated inflammatory signaling. Conclusion Serum exosomal AC245100.4 is a promising biomarker for the early diagnosis and prognostic stratification of AP and may complement existing clinical risk assessment tools. Its association with inflammation-related intercellular signaling also provides mechanistic support for its relevance in AP progression.