Potential Microrna Biomarker Panel for Predicting Evolution of Pancreatitis to Pancreatic Ductal Adenocarcinoma

Overview

PDAC (pancreatic ductal adenocarcinoma) is the 3rd most common cause of cancer deaths and is projected to be the 2nd most common cause by 2030 even as it comprises only 3.2% of all cancer cases. The most important predictor of survival is resection of earl y-stage cancer. PDAC risk is 15 -16 fold for chronic pancreatitis. A differentially expressed microRNA (DEM) serum panel is identified, compared, and extracted that could predict risk of progression to PDAC from pancreatitis. Two microarray Genomic Spatial Event (GSE) datasets containing pancreatitis, PDAC, and control samples were used to extract DEM common to both pancreatitis and PDAC. 8 smaller subgroups of DEM were derived from bioinformatics methods such as ROC/AUC of expression values, up and downreg ulated clustering, correlation analysis, miRNA interaction networks, target gene prediction tools, target gene interaction and functional enrichment analysis for all target genes and top modules, as well as decision tree/cross -validated random forest machine learning models. The DEM original group (n=22) and the smaller subgroups predicted the risk of pancreatic cancer vs control in a validation set consisting of six other GSE datasets. The original 22miRNA panel had the highest accuracy, F1, precision and recall, followed by subgroup 6 derived from the target hub genes with the highest interaction (hsa -miR-28-3p, 320b, 320c, 320d, 532 -5p, and 423 -5p). A new serum microRNA biomarker panel predicting evolution of pancreatitis to pancreatic ductal adenocarcinoma, and its associated pathways, has been identified, that also performed well in distinguishing pancreatic cancer (with or without pancreatitis risk factor) from control.