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Unlocking the diagnostic power of plasma extracellular vesicle miR-200 family in pancreatic ductal adenocarcinoma
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Eleanor Rees,
Flora M. Upton,
Kate Bennett,
Catherine Blaker,
Benoit Immordino,
Annalisa Comandatore,
Luca Morelli,
Shivan Sivakumar,
Rutger-Jan Swijnenburg,
Marc G. Besselink,
Long R. Jiao,
Geert Kazemier,
Elisa Giovannetti ,
Jonathan Krell,
Adam E. Frampton
Journal of Experimental & Clinical Cancer Research, Volume: 43, Issue: 1
Swansea University Author:
Jason Webber
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© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License.
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DOI (Published version): 10.1186/s13046-024-03090-z
Abstract
BackgroundDistinguishing benign from malignant pancreaticobiliary disease is challenging because of the absence of reliable biomarkers. Circulating extracellular vesicles (EVs) have emerged as functional mediators between cells. Their cargos, including microRNAs (miRNAs), are increasingly acknowledg...
| Published in: | Journal of Experimental & Clinical Cancer Research |
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| ISSN: | 1756-9966 |
| Published: |
Springer Science and Business Media LLC
2024
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa67056 |
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| Abstract: |
BackgroundDistinguishing benign from malignant pancreaticobiliary disease is challenging because of the absence of reliable biomarkers. Circulating extracellular vesicles (EVs) have emerged as functional mediators between cells. Their cargos, including microRNAs (miRNAs), are increasingly acknowledged as an important source of potential biomarkers. This multicentric, prospective study aimed to establish a diagnostic plasma EV-derived miRNA signature to discriminate pancreatic ductal adenocarcinoma (PDAC) from benign pancreaticobiliary disease.MethodsPlasma EVs were isolated using size exclusion chromatography (SEC) and characterised using nanoparticle tracking analysis, electron microscopy and Western blotting. EV-RNAs underwent small RNA sequencing to discover differentially expressed markers for PDAC (n = 10 benign vs. 10 PDAC). Candidate EV-miRNAs were then validated in a cohort of 61 patients (n = 31 benign vs. 30 PDAC) by RT-qPCR. Logistic regression and optimal thresholds (Youden Index) were used to develop an EV-miR-200 family model to detect cancer. This model was tested in an independent cohort of 95 patients (n = 30 benign, 33 PDAC, and 32 cholangiocarcinoma).ResultsSmall RNA sequencing and RT-qPCR showed that EV-miR-200 family members were significantly overexpressed in PDAC vs. benign disease. Combined expression of the EV-miR-200 family showed an AUC of 0.823. In an independent validation cohort, application of this model showed a sensitivity, specificity and AUC of 100%, 88%, and 0.97, respectively, for diagnosing PDAC.ConclusionsThis is the first study to validate plasma EV-miR-200 members as a clinically-useful diagnostic biomarker for PDAC. Further validation in larger cohorts and clinical trials is essential. These findings also suggest the potential utility in monitoring response and/or recurrence. |
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| Keywords: |
Biomarkers; Extracellular vesicles; Pancreatic ductal adenocarcinoma; microRNAs. |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
This research was funded by The Jon Moulton Charity Trust, UK (AEF); Action Against Cancer, UK (DKSL, MMP, ER, BP, LRJ, JK, AEF); the Royal College of Surgeons of Edinburgh, UK (AEF); the Royal College of Surgeons of England (AEF, DSKL); the Mason Medical Research Foundation, UK (AEF); the S.A.L. Charitable Fund, UK (AEF); BRIGHT cancer charity (AEF, BYP); the Bennink Foundation, the Netherlands (JRP, GK, EG); Italian Association for Cancer Research AIRC, Italy (EG); PANOMIC grant by Fondazione Pisa (AC, LM, EG); Fondazione Pisana Per La Scienza, Italy (EG); and the Dutch Cancer Society KWF (RJS, EG, GK). |
| Issue: |
1 |