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• W2885332214 abstract "Accurate diagnosis of lesions in the pancreatic head is a challenge with substantial clinical consequences in daily practice. Located in the pancreatic head, both distal cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC) are highly lethal malignancies with limited but distinct therapeutic options. Given these different therapeutic considerations, discovery of novel biomarkers that can ensure differential diagnostic specificity is an unmet clinical need. This study aims to identify a circulating microRNA (miRNA) signature to accurately diagnose and discriminate distal CCA from PDAC. In the initial discovery phase, microarray profiling of a panel of 752 miRNAs was performed on seven distal CCA and seven age- and sex-matched healthy control plasma samples. Raw data were normalized to the global mean. Based on probability value and fold change, candidate miRNAs were selected for further validation. In the validation phase, selected candidate miRNAs were analyzed in an independent cohort of distal CCA (n = 22) and healthy controls (n = 32) using RT-qPCR. To further assess the origin of lesions, candidate miRNA expression profiles were analyzed in malignant disease (n = 90) compared to benign disease (n = 15), and distal CCA (n = 22) compared to PDAC (n = 30). Following an empirically based selection of potential reference genes, raw data were normalized to a combination of two normalizing reference miRNAs. In the discovery phase, microarray analysis revealed nineteen miRNAs that were significantly deregulated in patients with distal CCA compared to healthy controls. Thirteen miRNAs were selected for further validation. In the validation phase, using logistic regression analysis, a three-miRNA panel was identified as the most robust diagnostic signature to discriminate malignant from benign disease (AUC = 0.881). Remarkably, two miRNAs of this panel were validated as specific classifier for distal CCA, with an AUC of 0.814 in differentiating distal CCA from PDAC. In addition, a combination of miR-93 and miR-101 was used as bona fide normalizing reference gene for these analyses. In conclusion, a combined panel of plasma miRNAs shows promising diagnostic capability to serve as unique minimally invasive distal CCA biomarker and has the potential to help clinical decision making for patients affected by pancreatobiliary disease in the pancreatic head. Citation Format: Jisce R. Puik, Laura L. Meijer, Tessa Y. Le Large, Michal Heger, Frederike Dijk, Niccola Funel, Ingrid Garajova, Elisa Giovannetti, Geert Kazemier. Circulating biliary tract microRNA signature discriminates cholangiocarcinoma from pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 493." @default.
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• W2885332214 date "2018-07-01" @default.
• W2885332214 modified "2023-10-15" @default.
• W2885332214 title "Abstract 493: Circulating biliary tract microRNA signature discriminates cholangiocarcinoma from pancreatic cancer" @default.
• W2885332214 doi "https://doi.org/10.1158/1538-7445.am2018-493" @default.
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