Oncotarget

Research Papers:

Prospective validation of microRNA signatures for detecting pancreatic malignant transformation in endoscopic-ultrasound guided fine-needle aspiration biopsies

Adam E. Frampton, Jonathan Krell, Mireia Mato Prado, Tamara M.H. Gall, Nima Abbassi-Ghadi, Giovanna Del Vecchio Blanco, Niccola Funel, Elisa Giovannetti, Leandro Castellano, Mohamed Basyouny, Nagy A. Habib, Harry Kaltsidis, Panagiotis Vlavianos, Justin Stebbing and Long R. Jiao _

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Oncotarget. 2016; 7:28556-28569. https://doi.org/10.18632/oncotarget.8699

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Abstract

Adam E. Frampton1,2,*, Jonathan Krell2,*, Mireia Mato Prado2, Tamara M.H. Gall1, Nima Abbassi-Ghadi3, Giovanna Del Vecchio Blanco4, Niccola Funel5,6, Elisa Giovannetti5,6,7, Leandro Castellano2, Mohamed Basyouny1, Nagy A. Habib1, Harry Kaltsidis8, Panagiotis Vlavianos8, Justin Stebbing2,#, Long R. Jiao1,#

1HPB Surgical Unit, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, UK

2Division of Cancer, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, UK

3Academic Surgical Unit, Department of Surgery and Cancer, Imperial College, St. Mary's Hospital, London, UK

4Department of Systems Medicine, Gastroenterology Unit, University Tor Vergata, Rome, Italy

5Cancer Pharmacology Lab, AIRC Start-Up Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy

6CNR-Nano, Institute of Nanoscience and Nanotechnology, Pisa, Italy

7Department of Medical Oncology, VU University Medical Center, Amsterdam, Netherlands

8Department of Gastroenterology, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK

*These authors share co-first authorship

#These authors share co-senior authorship

Correspondence to:

Long R. Jiao, e-mail: [email protected]

Keywords: microRNA, endoscopic ultrasound (EUS), fine-needle aspiration (FNA), pancreatic ductal adenocarcinoma, pancreatic cyst

Received: August 01, 2015     Accepted: March 22, 2016     Published: April 12, 2016

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.


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