Unlocking the diagnostic power of plasma extracellular vesicle miR-200 family in pancreatic ductal adenocarcinoma.
Biomarkers
Extracellular vesicles
Pancreatic ductal adenocarcinoma
microRNAs
Journal
Journal of experimental & clinical cancer research : CR
ISSN: 1756-9966
Titre abrégé: J Exp Clin Cancer Res
Pays: England
ID NLM: 8308647
Informations de publication
Date de publication:
08 Jul 2024
08 Jul 2024
Historique:
received:
27
02
2024
accepted:
06
06
2024
medline:
9
7
2024
pubmed:
9
7
2024
entrez:
8
7
2024
Statut:
epublish
Résumé
Distinguishing 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. Plasma 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). Small 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. This 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.
Sections du résumé
BACKGROUND
BACKGROUND
Distinguishing 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.
METHODS
METHODS
Plasma 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).
RESULTS
RESULTS
Small 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.
CONCLUSIONS
CONCLUSIONS
This 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.
Identifiants
pubmed: 38978141
doi: 10.1186/s13046-024-03090-z
pii: 10.1186/s13046-024-03090-z
doi:
Substances chimiques
MicroRNAs
0
MIRN200 microRNA, human
0
Biomarkers, Tumor
0
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
189Subventions
Organisme : Jon Moulton Charity Trust
ID : Jon Moulton Charity Trust
Organisme : Action Against Cancer
ID : Action Against Cancer
Organisme : Action Against Cancer
ID : Action Against Cancer
Organisme : Action Against Cancer
ID : Action Against Cancer
Organisme : Action Against Cancer
ID : Action Against Cancer
Organisme : Action Against Cancer
ID : Action Against Cancer
Organisme : Action Against Cancer
ID : Action Against Cancer
Organisme : Action Against Cancer
ID : Action Against Cancer
Organisme : Royal College of Surgeons of Edinburgh
ID : Royal College of Surgeons of Edinburgh
Organisme : Royal College of Surgeons of England
ID : Royal College of Surgeons of England
Organisme : Royal College of Surgeons of England
ID : Royal College of Surgeons of England
Organisme : Mason Medical Research Trust
ID : Mason Medical Research Trust
Organisme : S.A.L. Charitable Fund
ID : S.A.L. Charitable Fund
Organisme : BRIGHT Cancer Charity
ID : BRIGHT Cancer Charity
Organisme : BRIGHT Cancer Charity
ID : BRIGHT Cancer Charity
Organisme : Bennink Foundation
ID : Bennink Foundation
Organisme : Bennink Foundation
ID : Bennink Foundation
Organisme : Bennink Foundation
ID : Bennink Foundation
Organisme : Italian Association of Cancer Research AIRC
ID : Italian Association of Cancer Research AIRC
Organisme : Fondazione Pisa
ID : PANOMIC grant
Organisme : KWF Kankerbestrijding
ID : KWF Kankerbestrijding
Organisme : KWF Kankerbestrijding
ID : KWF Kankerbestrijding
Organisme : KWF Kankerbestrijding
ID : KWF Kankerbestrijding
Informations de copyright
© 2024. The Author(s).
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