TY  - JOUR
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive carcinoma entities worldwide with early and rapid dissemination. Recently, we discussed the role of microRNAs as epigenetic regulators of Epithelial-to-Mesenchymal Transition (EMT) in PDAC. In this study, we investigated their value as diagnostic and prognostic markers in tissue and blood samples of 185 patients including PDAC, non-malignant pancreatic disorders, and age-matched healthy controls. Expression of the microRNA-200-family (microRNAs -141, -200a, -200b, -200c, -429) and microRNA-148a was significantly downregulated in tissue of PDAC Union internationale contre le cancer (UICC) Stage II. Correspondingly, stromal PDAC tissue showed strong expression of Fibronectin, Vimentin, and ZEB-1 (Zinc finger E-box-binding homeobox) versus low expression of E-cadherin. Transient transfection of microRNA-200b and microRNA-200c mimics resulted in the downregulation of their key target ZEB-1. Inversely, blood serum analyses of patients with PDAC UICC Stages II, III, and IV showed a significant over-expression of microRNA-200-family members, microRNA-148a, microRNA-10b, and microRNA-34a. Correspondingly, Enzyme-linked Immunosorbent Assay (ELISA) analyses revealed a significant over-expression of soluble E-cadherin in serum samples of PDAC patients versus healthy controls. The best diagnostic accuracy to distinguish between PDAC and non-PDAC in this patient collective could be achieved in tissue by microRNA-148a with an area under the receiver-operating-characteristic (ROC) curve (AUC) of 0.885 and in blood serum by a panel of microRNA-141, -200b, -200c, and CA.19-9 with an AUC of 0.890. Both diagnostic tools outreach the diagnostic performance of the currently most common diagnostic biomarker CA.19-9 (AUC of 0.834). Kaplan Meier survival analysis of this patient collective revealed an improved overall survival in PDAC patients with high expression of tissue-related microRNA-34a, -141, -200b, -200c, and -429. In conclusion, EMT-regulating microRNAs have great potential as liquid and solid biopsy markers in PDAC patients. Their prognostic and therapeutic benefits remain important tasks for future studies.
AU  - Dhayat, Sameer
AU  - Träger, Max M.
AU  - Rehkämper, Jan
AU  - Ströse, Anda Jana
AU  - Steinestel, Konrad Ernst
AU  - Wardelmann, Eva
AU  - Kabar, Iyad
AU  - Senninger, Norbert
DA  - 2018-09-13
DO  - 10.3390/cancers10090328
KW  - pancreatic ductal adenocarcinoma
KW  - epithelial-to-mesenchymal transition
KW  - microRNA
KW  - biomarker
KW  - epigenetics
LA  - eng
N1  - Cancers 10 (2018) 9, 328, 1-20
N1  - Finanziert durch den Open-Access-Publikationsfonds 2018 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
PY  - 2018-09-13
TI  - Clinical Impact of Epithelial-to-Mesenchymal Transition Regulating MicroRNAs in Pancreatic Ductal Adenocarcinoma
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:6-24149555312
Y2  - 2024-11-22T02:01:45
ER  -