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

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.

Omics Analysis of Educated Platelets in Cancer and Benign Disease of the Pancreas

“…In Figure 3 A, we show the mRNA transcript SPARC is negatively correlated to several isomiRs, namely miR-17-3p, miR-29a-3p, miR-22-3p and miR-221-5p, while panel B shows canonical miRNAs associated to SPARC modulation that are not significantly different between PDAC and benign blood platelets included in our study. Of note, high expression of miR-22-3p is associated to poor survival in an external cohort of PDAC patients ( Figure S3 ) as reported previously [ 45 ]. Moreover, KEGG pathways analysis of the above-mentioned miRNAs revealed an enrichment of classical PDAC pathways such as PI3K-Akt signaling, mTOR pathway, focal adhesion and “pancreatic cancer pathways” itself ( Table S2 ).…”

“…Ontology mining for those miRNAs revealed an over-expression of classical PDAC pathways, such as ErbB signaling, PI3K-Akt signaling, mTOR pathway, focal adhesion. Notably, high plasma levels of miR-22 appear to be prognostic for poor survival in an external PDAC cohort [ 45 ]. However, a clear relationship between miR-22 and SPARC has not yet been described.…”

A Novel Serum Metabolomic Profile for the Differential Diagnosis of Distal Cholangiocarcinoma and Pancreatic Ductal Adenocarcinoma

“…In recent years, several studies have proposed circulating microRNA (miRNA) signatures for early detection of pancreatic cancer [31] or for the differential diagnosis of PDAC and chronic pancreatitis with good sensitivity and specificity [32], although none of them included a group of patients with pancreatic cysts. A recent study proposed a two-miRNA panel of downregulated miR-16 and upregulated miR-877 to differentiate patients with dCCA from benign disease (AUC = 0.90) and from PDAC (AUC = 0.88) [33]. Serum proteins have also been investigated.…”

Omics-Based Platforms: Current Status and Potential Use for Cholangiocarcinoma

“…However, they have established a microarray profile containing blank and MC-LR after 24 h of treatment in Huh28 cells. Meijer distinguished the circulating miR-16 and miR-877 as the diagnostic classifiers for eCCA (GSE117687) [ 86 ].…”