Efficient Identification of miRNAs for Classification of Tumor Origin

Rolf Søkilde, Martin Vincent, Anne K Møller, Alastair Hansen, Poul E Høiby, Thorarinn Blondal, Boye S Nielsen, Gedske Daugaard, Søren Møller, Thomas Litman

45 Citationer (Scopus)

Abstract

Carcinomas of unknown primary origin constitute 3% to 5% of all newly diagnosed metastatic cancers, with the primary source difficult to classify with current histological methods. Effective cancer treatment depends on early and accurate identification of the tumor; patients with metastases of unknown origin have poor prognosis and short survival. Because miRNA expression is highly tissue specific, the miRNA profile of a metastasis may be used to identify its origin. We therefore evaluated the potential of miRNA profiling to identify the primary tumor of known metastases. Two hundred eight formalin-fixed, paraffin-embedded samples, representing 15 different histologies, were profiled on a locked nucleic acid-enhanced microarray platform, which allows for highly sensitive and specific detection of miRNA. On the basis of these data, we developed and cross-validated a novel classification algorithm, least absolute shrinkage and selection operator, which had an overall accuracy of 85% (CI, 79%-89%). When the classifier was applied on an independent test set of 48 metastases, the primary site was correctly identified in 42 cases (88% accuracy; CI, 75%-94%). Our findings suggest that miRNA expression profiling on paraffin tissue can efficiently predict the primary origin of a tumor and may provide pathologists with a molecular diagnostic tool that can improve their capability to correctly identify the origin of hitherto unidentifiable metastatic tumors and, eventually, enable tailored therapy.
OriginalsprogEngelsk
TidsskriftThe Journal of molecular diagnostics : JMD
Vol/bind16
Udgave nummer1
Sider (fra-til)106-15
Antal sider10
ISSN1525-1578
DOI
StatusUdgivet - jan. 2014

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