The Complement and Coagulation Cascades Pathway is Associated with Acute Necrotizing Pancreatitis by Genomics and Proteomics Analysis.

Abstract

PurposeAcute pancreatitis can be classified histologically as interstitial edema pancreatitis (IEP) or as acute necrotizing pancreatitis (ANP). ANP has a higher mortality and long-term or short-term sequelae than IEP. Therefore, this work aims to explore the differences in pathogenesis between ANP and IEP and it has great clinical importance for the treatment and prevention of ANP.MethodsIn this work, whole blood samples from IEP and ANP patients were analyzed by whole gene sequencing (WGS). Serum samples from IEP and ANP patients were evaluated via enzyme-linked immunosorbent assay (ELISA). Meanwhile, pancreatic tissues of IEP and ANP rat models were subjected to data independent acquisition (DIA) proteomics assays. Then, the WGS analysis and DIA proteomics assay data were analyzed comprehensively.ResultsSix pathways were found to be significantly different in the ANP/IEP groups through WGS analysis. DIA proteomics found eleven different pathways. In both assays, the complement and coagulation cascades pathway was the most significantly different (p < 0.01) pathway between the two groups. WGS analysis showed base mutations in ten genes in the complement and coagulation cascades pathway. These results were consistent with the ten proteins detected by DIA proteomics analysis, which were significantly upregulated in the ANP/IEP groups. In addition, five of these proteins, complement C3, complement Factor I, alpha-2-macroglobulin, complement C9, and serpin family C member 1, were successfully verified by parallel reaction monitoring analysis and ELISA.ConclusionC3, CFI, A2m, C9, and Serpinc1, which belong to complement and coagulation cascades pathway, may promote pancreatic necrosis and aggravate the severity of ANP.