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.
Highlights
Adenocarcinomas located in the pancreatic head can be classified as either distal cholangiocarcinoma (CCA) or pancreatic ductal adenocarcinoma (PDAC) [1]
Patients with distal CCA and healthy individuals included in the discovery phase were age- and sex-matched
In the evaluation and validation phase, age of patients with benign disease (BD) was lower compared to distal CCA and PDAC
Summary
Adenocarcinomas located in the pancreatic head can be classified as either distal cholangiocarcinoma (CCA) or pancreatic ductal adenocarcinoma (PDAC) [1]. These malignancies show considerable overlap in diagnostic features as patients present with similar symptoms and an indistinguishable mass on imaging modalities [2]. CCA is classified as CCA based on its anatomic location and treated in analogy with intrahepatic and perihilar CCA [2,6] These subtypes have distinct biologic behavior and should be considered as individual tumor types [7,8]. Resection of the primary tumor is still the only curative treatment option, neo-adjuvant treatment strategies are gaining momentum and this urges the need for accurate minimally invasive diagnostic tools
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