Plasma MicroRNA Biomarkers in Limited Volume Samples for Detection of Early Stage Pancreatic Cancer.

Early detection of pancreatic ductal adenocarcinoma (PDAC) is key to improving patient outcomes; however, PDAC is usually diagnosed late. Therefore, blood-based minimally invasive biomarker assays for limited volume clinical samples are urgently needed. A novel microRNA profiling platform (Abcam Fireplex-Oncology Panel) was used to investigate the feasibility of developing early detection miRNA biomarkers with 20ul plasma from a training set (58 stage II PDAC cases and 30 controls) and two validation sets (34 stage II PDAC cases and 25 controls; 44 stage II PDAC cases and 18 controls). miR-34a-5p (AUC = 0.77, 95% CI 0.66 to 0.87), miR-130a-3p (AUC = 0.74, 95% CI 0.63 to 0.84,), and miR-222-3p (AUC = 0.70, 95% CI 0.58 to 0.81,) were identified as significantly differentially abundant in plasma from stage II PDAC vs. controls. Although none of the miRNAs individually outperformed the currently used serological biomarker for PDAC, CA19-9, combining the miRNAs with CA 19-9 improved AUCs from 0.89 (95% CI 0.81 to 0.95) for CA 19-9 alone to 0.92 (95% CI 0.86 to 0.97), 0.94 (95% CI 0.89 to 0.98), and 0.92 (95% CI 0.87 to 0.97), respectively. Gene Set Enrichment Analyses of transcripts correlated with high and low expression of the three miRNAs in the TCGA PDAC sample set. These miRNA biomarkers, assayed in limited volume plasma together with CA19-9, discriminate stage II PDAC from controls with good sensitivity and specificity. Unbiased profiling of larger cohorts should help develop an informative early detection biomarker assay for diagnostic settings.