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dc.contributor.authorQuiohilag, Katherine
dc.contributor.authorCaie, Peter
dc.contributor.authorOniscu, Anca
dc.contributor.authorBrenn, Thomas
dc.contributor.authorHarrison, David
dc.date.accessioned2020-05-25T15:30:04Z
dc.date.available2020-05-25T15:30:04Z
dc.date.issued2020-05-09
dc.identifier268138679
dc.identifier68b10981-7415-4ead-94f5-4ef153db3bfa
dc.identifier85084517717
dc.identifier32388720
dc.identifier000531216100001
dc.identifier.citationQuiohilag , K , Caie , P , Oniscu , A , Brenn , T & Harrison , D 2020 , ' The differential expression of micro-RNAs 21, 200c, 204, 205, and 211 in benign, dysplastic and malignant melanocytic lesions and critical evaluation of their role as diagnostic biomarkers ' , Virchows Archiv , vol. First Online . https://doi.org/10.1007/s00428-020-02817-5en
dc.identifier.issn0945-6317
dc.identifier.otherORCID: /0000-0001-9041-9988/work/74873026
dc.identifier.otherORCID: /0000-0002-0031-9850/work/74873056
dc.identifier.urihttps://hdl.handle.net/10023/19991
dc.description.abstractOverlapping histological features between benign and malignant lesions and a lack of firm diagnostic criteria for malignancy result in high rates of inter-observer variation in the diagnosis of melanocytic lesions. We aimed to investigate the differential expression of five miRNAs (21, 200c, 204, 205, and 211) in benign naevi (n = 42), dysplastic naevi (n = 41), melanoma in situ (n = 42), and melanoma (n = 42) and evaluate their potential as diagnostic biomarkers of melanocytic lesions. Real-time PCR showed differential miRNA expression profiles between benign naevi; dysplastic naevi and melanoma in situ; and invasive melanoma. We applied a random forest machine learning algorithm to classify cases based on their miRNA expression profiles, which resulted in a ROC curve analysis of 0.99 for malignant melanoma and greater than 0.9 for all other groups. This indicates an overall very high accuracy of our panel of miRNAs as a diagnostic biomarker of benign, dysplastic, and malignant melanocytic lesions. However, the impact of variable lesion percentage and spatial expression patterns of miRNAs on these real-time PCR results was also considered. In situ hybridisation confirmed the expression of miRNA 21 and 211 in melanocytes, while demonstrating expression of miRNA 205 only in keratinocytes, thus calling into question its value as a biomarker of melanocytic lesions. In conclusion, we have validated some miRNAs, including miRNA 21 and 211, as potential diagnostic biomarkers of benign, dysplastic, and malignant melanocytic lesions. However, we also highlight the crucial importance of considering tissue morphology and spatial expression patterns when using molecular techniques for the discovery and validation of new biomarkers.
dc.format.extent10
dc.format.extent849085
dc.language.isoeng
dc.relation.ispartofVirchows Archiven
dc.subjectDermatopathologyen
dc.subjectMelanomaen
dc.subjectmicroRNAen
dc.subjectMolecular pathologyen
dc.subjectRB Pathologyen
dc.subjectPathology and Forensic Medicineen
dc.subjectMolecular Biologyen
dc.subjectCell Biologyen
dc.subjectDASen
dc.subject.lccRBen
dc.titleThe differential expression of micro-RNAs 21, 200c, 204, 205, and 211 in benign, dysplastic and malignant melanocytic lesions and critical evaluation of their role as diagnostic biomarkersen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews. Sir James Mackenzie Institute for Early Diagnosisen
dc.contributor.institutionUniversity of St Andrews. Centre for Biophotonicsen
dc.contributor.institutionUniversity of St Andrews. Cellular Medicine Divisionen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.identifier.doi10.1007/s00428-020-02817-5
dc.description.statusPeer revieweden


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