Pancreatic ductal
adenocarcinoma (PDAC) is known for its poor prognosis resulting from being diagnosed at an advanced stage. Accurate early diagnosis and new therapeutic modalities are therefore urgently needed.
MicroRNAs (
miRNAs), considered a new class of
biomarkers and therapeutic targets, may be able to fulfill those needs. Combining tissue microdissection with global
miRNA array analyses, cell type-specific
miRNA expression profiles were generated for normal pancreatic ductal cells, acinar cells, PDAC cells derived from xenografts and also from macrodissected
chronic pancreatitis (CP) tissues. We identified 78
miRNAs differentially expressed between ND and PDAC cells providing new insights into the
miRNA-driven pathophysiological mechanisms involved in PDAC development. Having filtered
miRNAs which are upregulated in the three pairwise comparisons of PDAC vs. ND, PDAC vs. AZ and PDAC vs. CP, we identified 15
miRNA biomarker candidates including miR-135b. Using relative qRT-PCR to measure miR-135b normalized to miR-24 in 75 FFPE specimens (42 PDAC and 33 CP) covering a broad range of
tumor content, we discriminated CP from PDAC with a sensitivity and specificity of 92.9% [95% CI=(80.5, 98.5)] and 93.4% [95% CI=(79.8, 99.3)], respectively. Furthermore, the area under the curve (AUC) value reached of 0.97 was accompanied by positive and negative predictive values of 95% and 91%, respectively. In conclusion, we report pancreatic cell-specific global
miRNA profiles, which offer new candidate
miRNAs to be exploited for functional studies in PDAC. Furthermore, we provide evidence that
miRNAs are well-suited analytes for development of sensitive and specific aid-in-diagnosis tests for PDAC.