Dataset Information

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

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Pancreatic ductal adenocarcinoma (PDAC) suffers from lack of an effective diagnostic method, limiting improvement in patient survival. Although the FDA-approved biomarker CA19-9 has been used for detection and surveillance of PDAC, its clinical utility is generally regarded to be limited due to its suboptimal diagnostic performance. Liquid chromatography-mass spectrometry (LC-MS) has emerged as a burgeoning technology in clinical proteomics, and identified a plethora of protein biomarker candidates for PDAC. Yet few if any has successfully transitioned into clinical practice. This translational standstill is owed partly to the limited considerations of practical needs and perspectives of clinical implementation in the course of a biomarker pipeline, such as demonstrating analytical validity of proposed biomarkers, which is critical to turning research-grade assays to clinical-grade tests. Here, we developed a fit-for-purpose multi-marker panel for PDAC diagnosis by consolidating analytically robust biomarkers as well as employing a relatively simple LC-MS method. In the discovery phase, we systematically collected putative biomarkers from both in-house proteomics data and the large volume of literature documenting PDAC biomarkers. In the verification phase, we developed a multiple-reaction monitoring (MRM)-MS-based proteomic assay using surrogate peptides that passed stringent analytical validation criteria. Given the intended use of our panel (i.e., primary screening), we adopted a high-throughput protocol including short gradient (<10 min) and simple sample preparation (no depletion or enrichment steps). To further facilitate clinical implementation, we performed verification of our panel on serum samples, which are usually the preferred biospecimen available in clinical settings. We developed a stacking ensemble model based on our final panel of 12 protein biomarkers combined with CA19-9, which showed improved diagnostic performance compared to using CA19-9 alone (AUC 0.919 and 0.830, respectively). A large-scale clinical validation study is underway to demonstrate the clinical validity of our panel.

Dataset Information

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

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets