Prospective validation of microRNA signatures for detecting pancreatic malignant transformation in endoscopic-ultrasound guided fine-needle aspiration biopsies
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. Novel
biomarkers are required to aid treatment decisions and improve patient outcomes.
MicroRNAs (miRNAs) are potentially ideal diagnostic biomarkers, as they are stable
molecules, and tumour and tissue specific.
Results: Logistic regression analysis revealed an endoscopic-ultrasound fine-
needle aspiration (EUS-FNA) 2-miRNA classifier (miR-21 + miR-155) capable
of distinguishing benign from malignant pancreatic lesions with a sensitivity of
81.5% and a specificity of 85.7% (AUC 0.930). Validation FNA cohorts confirmed
both miRNAs were overexpressed in malignant disease, while circulating miRNAs
performed poorly.
Methods: Fifty-five patients with a suspicious pancreatic lesion on cross-sectional
imaging were evaluated by EUS-FNA. At echo-endoscopy, the first part of the FNA was
sent for cytological assessment and the second part was used for total RNA extraction.
Candidate miRNAs were selected after careful review of the literature and expression
was quantified by qRT-PCR. Validation was performed on an independent cohort of
EUS-FNAs, as well as formalin-fixed paraffin embedded (FFPE) and plasma samples.
Conclusions: We provide further evidence for using miRNAs as diagnostic
biomarkers for pancreatic malignancy. We demonstrate the feasibility of using fresh
EUS-FNAs to establish miRNA-based signatures unique to pancreatic malignant
transformation and the potential to enhance risk stratification and selection for
surgery.
biomarkers are required to aid treatment decisions and improve patient outcomes.
MicroRNAs (miRNAs) are potentially ideal diagnostic biomarkers, as they are stable
molecules, and tumour and tissue specific.
Results: Logistic regression analysis revealed an endoscopic-ultrasound fine-
needle aspiration (EUS-FNA) 2-miRNA classifier (miR-21 + miR-155) capable
of distinguishing benign from malignant pancreatic lesions with a sensitivity of
81.5% and a specificity of 85.7% (AUC 0.930). Validation FNA cohorts confirmed
both miRNAs were overexpressed in malignant disease, while circulating miRNAs
performed poorly.
Methods: Fifty-five patients with a suspicious pancreatic lesion on cross-sectional
imaging were evaluated by EUS-FNA. At echo-endoscopy, the first part of the FNA was
sent for cytological assessment and the second part was used for total RNA extraction.
Candidate miRNAs were selected after careful review of the literature and expression
was quantified by qRT-PCR. Validation was performed on an independent cohort of
EUS-FNAs, as well as formalin-fixed paraffin embedded (FFPE) and plasma samples.
Conclusions: We provide further evidence for using miRNAs as diagnostic
biomarkers for pancreatic malignancy. We demonstrate the feasibility of using fresh
EUS-FNAs to establish miRNA-based signatures unique to pancreatic malignant
transformation and the potential to enhance risk stratification and selection for
surgery.
Date Issued
2016-04-12
Date Acceptance
2016-03-23
Citation
Oncotarget, 2016, 7 (19)
ISSN
1949-2553
Publisher
Impact Journals
Journal / Book Title
Oncotarget
Volume
7
Issue
19
Copyright Statement
Licensed under a Creative Commons Attribution 3.0 License.
License URL
Sponsor
The Alliance Family Foundation
Grant Number
N/A
Subjects
Science & Technology
Life Sciences & Biomedicine
Oncology
Cell Biology
microRNA
endoscopic ultrasound (EUS)
fine-needle aspiration (FNA)
pancreatic ductal adenocarcinoma
pancreatic cyst
DUCTAL ADENOCARCINOMA
CYST FLUID
PREOPERATIVE DIAGNOSIS
CLINICAL-SIGNIFICANCE
EXPRESSION
NEOPLASMS
CANCER
MANAGEMENT
SURVIVAL
LESIONS
Publication Status
Published
Article Number
28556