The Study For The Genomics And Proteomics Of Acute Pancreatitis Based On Imaging Classification

Background:Acute pancreatitis can be classified histologically as interstitial edema pancreatitis(IEP)or as acute necrotizing pancreatitis(ANP).In clinical practice,AP can also be classified into IEP and ANP according to their imaging features.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,which may has great clinical importance for the treatment and prevention of ANP.Objective:In this paper,AP is divided into ANP and IEP through imaging studies,and the differences between ANP and IEP in pathological mechanism are studied through genomics and proteomics,in order to provide guidance for the clinical treatment of ANP and the development of specific drugs.Method:A total of 47 AP patients were enrolled and divided into IEP group(n=21)and ANP group(n=26)according to the imaging findings of abdominal enhanced CT/MR examination.And whole blood samples from IEP and ANP patients were analyzed by whole gene sequencing(WGS).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.Then serum samples from IEP and ANP patients were detected via enzyme-linked immunosorbent assay(ELISA)to verify the screened proteins.Result:Imaging analysis showed that CTSI/MRSI score and RAC based severity of patients in ANP group were significantly higher than those in IEP group(P<0.05).Six 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.Some of the genes with base mutations in complement and coagulation cascades pathway identified by WGS analysis were consistent with the proteins detected by DIA proteomics,which were significantly upregulated in 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.Conclusion:CTSI/MRSI score and RAC based severity were significantly higher in the ANP group than in the IEP group,suggesting that CTSI/MRSI score can effectively assess the severity of AP.Complement and coagulation cascades pathway can promote pancreatic necrosis,thereby exacerbating the severity and inflammatory response of AP.