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Unravelling the diagnostic dilemma of pancreatic head lesions: A circulating microRNA panel to diagnose distal cholangiocarcinoma

ABSTRACT: Introduction: Accurate diagnosis of distal cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC) is a challenge with clinical consequences. Both are lethal malignancies with distinct therapeutic options. This study aimed to identify a circulating microRNA (miRNA) signature to diagnose and discriminate distal CCA from PDAC. Methods: In the discovery phase, microarray profiling of 752 miRNAs was performed on plasma samples of seven patients with distal CCA and seven age- and sex-matched healthy controls. Significant candidate miRNAs were selected for validation based on predefined selection criteria. In the validation phase, these miRNAs were analyzed by RT-qPCR in an independent cohort of healthy controls (n=32), benign periampullary disease (n=20), distal CCA (n=24), and age- sex- and stage-matched PDAC (n=24). Data were normalized to a combination of two reference genes. The optimal diagnostic combination of miRNAs was determined by logistic regression. Sensitivity and specificity were evaluated by ROC curves and AUC values. Results: In the discovery phase, 19 miRNAs were significantly deregulated in patients with distal CCA compared to healthy controls. In the validation phase, 12 candidate miRNAs were selected for validation by RT-qPCR based on pre-defined selection criteria. A two-miRNA panel of downregulated miR-16 and upregulated miR-877 was able accurately distinguish distal CCA from benign disease as well as from PDAC. Conclusion: This is the first study to identify a combined panel of plasma miRNAs which shows promising diagnostic capability to serve as distal CCA signature with the potential to discriminate distal CCA from PDAC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE117687 | GEO | 2019/11/26

REPOSITORIES: GEO

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