Analysis Of MiRNA-mRNA Regulation Network And Screening And Identification Of MiRNA Biomarkers For Early Diagnosis In Patients With Chronic Pancreatitis

Part one Analysis of miRNA-mRNA regulation network of chronic pancreatitisObjective:To explore the underlying molecular mechanisms and potential molecular biomarkers of chronic pancreatitis(CP)and construct a miRNA-mRNA regulation network to guide clinical diagnosis and treatment of CP.Methods:We downloaded the miRNA and mRNA expression profiles of CP patients and healthy controls from Gene Expression Atlas and identified the differentially expressed miRNAs and genes.Functional analysis was conducted and significant pathways were utilized.Finally,the miRNA-mRNA regulation network of CP was constructed.Results:A total of 44 miRNA-risk gene-pathway relationships were identified,and a complex regulation network was constructed with three genes(ABL1,MYC and ANAPC13)having the highest degree in affecting the network of CP.Importantly,four risk genes(NOTCH3,COX5 A,THBS1 and KARS)and one risk miRNA(hsa-miR-324-5p)were identified with high prediction accuracy.Conclusion:In conclusion,we analyzed miRNA and mRNA expression profiles in CP,one risk miRNA(hsa-miR-324-5p)and four risk genes(NOTCH3?COX5A?THBS1 and KARS)were identified with high prediction accuracy as biomarkers of CP.Although further confirmation in clinical study is needed,our findings provide new insights into the pathogenesis of CP and may improve the diagnosis and therapy by identifying novel targets.Part two Screening and Identification of blood-based miRNA biomarker panel for early diagnosis of chronic pancreatitisObjective:Chronic pancreatitis(CP)is a common pancreatic disease,with features of irreversible morphologic injury as well as fibrosis.Early diagnosis and treatment will improve the pancreatic function and upgrade the quality of life.MiRNAs are applied as diagnostic or prognostic markers for many diseases.However,few studies have described biomarkers for the diagnosis or prediction of early CP.Our study aims to explore the specific serum miRNAs of CP and construct a novel blood-based miRNA biomarker panel for early diagnosis of CP.Methods:In the current study,we analyzed the differentially expressed miRNAs(DEmiRs)of CP patients from Gene Expression Omnibus(GEO)by bioinformatics methods,took blood from 10 early CP patients,10 late CP patients and 18 controls to confirm the results,and compared the DEmiRs in plasma of early CP patients from the late ones by miRNA microarrays.Results:Our data showed that four DEmiRs(hsa-miR-320a/hsa-miR-320 b,and hsa-miR-320c/hsa-miR-320d)were obtained from GEO patients,however these miRNAs are more prone to predict late CP,but not early CP in clinical test.Early CP has distinct biomarkers,and two miRNAs(hsa-miR-221 and hsa-miR-130a)were obtained,with the prediction accuracies of 100% and 87.5% respectively.A combination of all above 6 miRNA biomarkers showed more sensitivity and specificity to diagnosis of CP.Our results also indicated that the miRNA expression profile showed difference in early and late CP.The integrated analysis and functional comparison revealed that the most impacted biological processes and associated signaling pathways were inconsistent between different stages of CP.Conclusion:In conclusion,biomarkers for each stage could not represent CP with different severity.And this panel of 6 serum miRNAs might have the potential to be used clinically as biomarkers for the early diagnosis and predicting CP.