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Unravelling the Diagnostic Dilemma: A MicroRNA Panel of Circulating MiR-16 and MiR-877 as A Diagnostic Classifier for Distal Bile Duct Tumors

1
Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, 1081 HV, The Netherlands
2
Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, 1081 HV, The Netherlands
3
Laboratory of Experimental Oncology and Radiobiology, Amsterdam UMC, University of Amsterdam, 1105 AZ, The Netherlands
4
Department of Experimental Surgery, Amsterdam UMC, University of Amsterdam, 1105 AZ, The Netherlands
5
Department of Pharmaceutics, Jiaxing University Medical College, Jiaxing 314001, Zhejiang, China
6
Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, 3584 CG, The Netherlands
7
Department of Pathology, Amsterdam UMC, University of Amsterdam, 1105 AZ, The Netherlands
8
Cancer Pharmacology Lab, AIRC Start-Up Unit, Fondazione Pisana per la Scienza onlus, 56017 Pisa, Italy
9
Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, 1081 HV, The Netherlands
10
Medical Oncology Unit, University Hospital of Parma, 43 126 Parma, Italy
11
Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, 1081 HV, The Netherlands
12
Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam UMC, VU University Amsterdam, 1081 HV, The Netherlands
*
Author to whom correspondence should be addressed.
Both authors contributed equally to this paper.
Both senior authors contributed equally to this paper.
Cancers 2019, 11(8), 1181; https://doi.org/10.3390/cancers11081181
Received: 16 July 2019 / Revised: 7 August 2019 / Accepted: 12 August 2019 / Published: 15 August 2019
(This article belongs to the Special Issue New Biomarkers in Cancers)
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Abstract

Accurate diagnosis of pancreatic head lesions remains challenging as no minimally invasive biomarkers are available to discriminate distal cholangiocarcinoma (CCA) from pancreatic ductal adenocarcinoma (PDAC). The aim of this study is to identify specific circulating microRNAs (miRNAs) to diagnose distal CCA. In the discovery phase, PCR profiling of 752 miRNAs was performed on fourteen patients with distal CCA and age- and sex-matched healthy controls. Candidate miRNAs were selected for evaluation and validation by RT-qPCR in an independent cohort of distal CCA (N = 24), healthy controls (N = 32), benign diseases (N = 20), and PDAC (N = 24). The optimal diagnostic combination of miRNAs was determined by multivariate logistic regression analysis and evaluated by ROC curves with AUC values. The discovery phase revealed 19 significantly dysregulated miRNAs, of which six were validated in the evaluation phase. The validation phase confirmed downregulated miR-16 in patients with distal CCA compared to benign disease or PDAC (P = 0.048 and P = 0.012), while miR-877 was significantly upregulated (P = 0.003 and P = 0.006). This two-miRNA panel was validated as a CCA-specific profile, discriminating distal CCA from benign disease (AUC = 0.90) and from PDAC (AUC = 0.88). In conclusion, the present study identified a two-miRNA panel of downregulated miR-16 and upregulated miR-877 with promising capability to diagnose patients with distal CCA. View Full-Text
Keywords: biliary tract cancer; distal cholangiocarcinoma; pancreatic cancer; diagnosis; biomarkers biliary tract cancer; distal cholangiocarcinoma; pancreatic cancer; diagnosis; biomarkers
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Meijer, L.L.; Puik, J.R.; Le Large, T.Y.; Heger, M.; Dijk, F.; Funel, N.; Wurdinger, T.; Garajová, I.; van Grieken, N.C.; van de Wiel, M.A.; Giovannetti, E.; Kazemier, G. Unravelling the Diagnostic Dilemma: A MicroRNA Panel of Circulating MiR-16 and MiR-877 as A Diagnostic Classifier for Distal Bile Duct Tumors. Cancers 2019, 11, 1181.

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