Abstract
IntroductionPancreatic cancer (PCA) is an aggressive tumor that associates with high mortality rates. Majority of PCA patients are diagnosed usually at late tumor stages when the therapeutic options are limited. MicroRNAs (miRNA) are involved in tumor development and are commonly dysregulated in PCA. As a proof-of-principle study, we aimed to evaluate the potential of fecal miRNAs as biomarkers for pancreatic cancer.Materials and MethodsTotal RNA was extracted from feces using Qiagen's miRNA Mini Kit. For miRNA expression analyses we selected a subset of 7 miRNAs that are frequently dysregulated in PCA (miR-21, -143, -155, -196a, -210, -216a, -375). Subsequently, expression levels of these miRNAs were determined in fecal samples from controls (n = 15), chronic pancreatitis (n = 15) and PCA patients (n = 15) using quantitative TaqMan-PCR assays.ResultsAll selected miRNAs were detectable in fecal samples with high reproducibility. Four of seven miRNAs (miR-216a, -196a, -143 und -155) were detected at lower concentrations in feces of PCA patients when compared to controls (p<0.05). Analysis of fecal miRNA expression in controls and patients with chronic pancreatitis and PCA revealed that the expression of miR-216a, -196a, -143 und -155 were highest in controls and lowest in PCA. The expression of the remaining three miRNAs (miR-21, -210 and -375) remained unchanged among controls and the patients with either chronic pancreatitis or PCA.ConclusionOur data provide novel evidence for the differential expression of miRNAs in feces of patients with PCA. If successfully validated in large-scale prospective studies, the fecal miRNA biomarkers may offer novel tools for PCA screening research.
Highlights
Pancreatic cancer (PCA) is an aggressive tumor that associates with high mortality rates
Expression levels of these miRNAs were determined in fecal samples from controls (n = 15), chronic pancreatitis (n = 15) and PCA patients (n = 15) using quantitative TaqMan-PCR assays
Four of seven miRNAs were detected at lower concentrations in feces of PCA patients when compared to controls (p,0.05)
Summary
Pancreatic cancer (PCA) is an aggressive tumor that associates with high mortality rates. Despite intensive basic and clinical research the median survival of patients with PCA remains approximately 6–10 months after diagnosis, which highlights the aggressive tumor biology of this disease [3]. Current clinical screening and diagnostic management of PCA patients is based on imaging techniques such as endoluminal ultrasound (EUS) or contrast-enhanced multi-detector CT scan. Due to their invasive nature, use of radiation, and low sensitivity/specificity, such techniques at best may only be used for the screening in highrisk patients (e.g. hereditary PCA, Peutz-Jeghers syndrome etc.)
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