MicroRNA biomarkers in whole blood for detection of pancreatic cancer.

Abstract

4052 Background: There is a great need for biomarkers for early diagnosis of patients with pancreatic cancer (PC) to improve their poor prognosis. The aims were (1) to describe differences in miRNA expression in whole blood between patients with PC, healthy subjects (HS) and patients with chronic pancreatitis (CP); and (2) to identify panels of miRNAs for early diagnosis of PC. Methods: Case-control study. 409 patients with PC, 33 patients with other periampullary cancers (PAC) and 25 patients with CP were included prospectively in the Danish BIOPAC biomarker study. 312 blood donors were included as HS. MiRNA expressions in pretreatment 2.5 ml whole blood samples collected in PAXgene RNA tubes were investigated in three independent cohorts: “Discovery Study” (PC n=143, CP n=18, HS n=69); “Training Study” (PC n=180, HS n=199); and “Validation Study” (PC n=86, PAC n=33, CP n=7, HS n=44). TaqMan Human MicroRNA assay was used to screen 754 miRNAs in the “Discovery Study”. Fluidigm BioMark PCR System was used in the “Training Study” (38 miRNAs) and “Validation Study” (13 miRNAs). Results: The “Discovery Study” demonstrated that 38 miRNAs (out of a total of 754 miRNAs) in whole blood were significantly deregulated between patients with PC and controls. These miRNAs were tested in the “Training Study” and two diagnostic indexes were constructed including 4 miRNAs in bPANmiRC index I (= miR-150 + miR-636 – miR-145 – miR-223) or 10 miRNAs in bPANmiRC index II (= 6.9275 – 0.2134xmiR-122 – 0.3560xmiR-34a – 0.8577xmiR-145 + 1.0043xmiR-636 – 0.6725xmiR-223 + 0.7018xmiR-26b – 0.3233xmiR-885.5p + 1.1304xmiR-150 – 0.2204xmiR-126* - 0.1730xmiR-505) (AUC 0.86/0.93, sensitivity 85%/85% and specificity 64%/85%). Conclusions: We identified two diagnostic indexes, using 4 or 10 miRNAs in peripheral whole blood, with a potential clinical value in the evaluation of patients with uncharacteristic symptoms to identify PC at an early stage.