Abstract

Diagnosis and treatment of pancreatic ductal adenocarcinoma (PA) remains a challenge in clinical practice. The aim of this study was to assess the role of microRNAs (miRNAs-21, -23a, -100, -107, -181c, -210) in plasma and tissue as possible biomarkers in the diagnosis of PA. Samples of plasma (PAp-n = 13), pancreatic tumors (PAt-n = 18), peritumoral regions (PPT-n = 9) were collected from patients during the surgical procedure. The control group consisted of samples from patients submitted to pancreatic surgery for trauma or cadaveric organs (PC-n = 7) and healthy volunteers donated blood (PCp-n = 6). The expression profile of microRNAs was measured in all groups using RT-PCR, serum CA19-9 levels were determined in PA and PC. In tissue samples, there was a difference in the expression of miRNAs-21, -210 (p < 0.05) across the PAt, PC and PPT groups. The PAp showed overexpression of miRNAs-181c, -210 (p < 0.05) when compared to PCp. The combination of miRNAs-21, -210 tissue expression and serum CA19-9 showed 100% accuracy in the diagnosis of PA, as well as miR-181c expression in the plasma (PApxPCp). The expression of microRNAs in plasma proved to be a promising tool for a noninvasive detection test for PA, as well as further studies will evaluate the utility of microRNAs expression as biomarkers for prognostic and response to therapy in PA.

Highlights

  • Pancreatic ductal adenocarcinoma (PA) represents only 2.8% of all new cases of cancer in the US [1]

  • We evaluated six miRNAs in PA tissue (PAt), peritumoral tissue (PPT), and control normal pancreatic tissue (PC)

  • Comparative analysis using the Dunn post-test showed that miRNA-21 discriminated between the PAt and the PC and peritumoral regions (PPT) groups and miRNA-210 discriminated between the PAt and PC groups (Table 2)

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Summary

Introduction

Pancreatic ductal adenocarcinoma (PA) represents only 2.8% of all new cases of cancer in the US [1]. PA is the fourth leading cause of cancer deaths and less than 5% of patients will survive for 5 years [2]. MicroRNAs (miRNAs) are a class of small noncoding RNAs consisting of 18–25 nucleotides that function by targeting specific mRNA for translational repression or degradation, thereby regulating several biological processes including cell proliferation, migration, invasion, survival, and metastasis. They act as negative regulators of the protein-coding gene expression by targeting mRNA [3] and due to their biological stability and role in cancer pathobiology, www.oncotarget.com miRNAs have a substantial potential as cancer biomarkers. Let-7a [14], miR-96 [15], miR-375 [16], miR-20a [17], and miR-200c [18] act as tumor suppressor miRNAs

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