Plasma proteomic profiling of septic shock and acute pancreatitis identifies shared signatures and disease-specific...

Septic shock represents the most severe form of infection-driven systemic inflammation, whereas acute pancreatitis induces a sterile inflammatory response. Although clinically similar, their molecular profiles may reveal distinct mechanisms underlying infectious and non-infectious inflammation. We performed plasma proteomic profiling using LC-MS/MS in patients with septic shock (n = 13), acute pancreatitis (n = 8), and healthy controls (n = 8). Among 663 quantified proteins, 231 were differentially expressed in septic shock versus controls, 83 in pancreatitis versus controls, and 29 in septic shock versus pancreatitis. Septic shock was characterized by higher plasma concentrations of MARCKS, HSP90AA1, PSAP, CD163, and GANAB, whereas pancreatitis showed higher levels of CPA1, APOC4, APOC3, BPGM, and APOC2. Cluster analysis demonstrated separation between groups, with overlapping proteomic patterns in sepsis and pancreatitis. Gene Ontology and KEGG analyses revealed shared inflammatory signatures, including upregulation of acute-phase responses and downregulation of coagulation pathways. However, septic shock exhibited more extensive proteomic alterations, with distinct activation of PI3K-Akt signaling and suppression of lipid metabolism. In conclusion, septic shock and pancreatitis share common inflammatory pathways, while proteomic differences highlight divergent regulation of coagulation, lipid metabolism, and anti-inflammatory signaling, offering potential biomarkers to distinguish infectious from sterile systemic inflammation.