A 10-gene classifier for indeterminate thyroid nodules: development and multicenter accuracy study

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dc.contributor.authorGonzález, Hernán
dc.contributor.authorMartínez, José R.
dc.contributor.authorVargas, Sergio
dc.contributor.authorSolar, Antonieta
dc.contributor.authorVéliz, Loreto
dc.contributor.authorCruz, Francisco
dc.contributor.authorArias, Tatiana
dc.contributor.authorLoyola, Soledad
dc.contributor.authorHorvath, Eleonora
dc.contributor.authorTala, Hernán
dc.contributor.authorTraipe, Eufrosina
dc.contributor.authorMeneses, Manuel
dc.contributor.authorMarín, Luis
dc.contributor.authorWohllk, Nelson
dc.contributor.authorDiaz, René
dc.contributor.authorVéliz, Jesús
dc.contributor.authorPineda, Pedro
dc.contributor.authorArroyo, Patricia
dc.contributor.authorMena, Natalia
dc.contributor.authorBracamonte, Milagros
dc.contributor.authorMiranda, Giovanna
dc.contributor.authorBruce, Elsa
dc.contributor.authorUrra, Soledad
dc.date.accessioned2018-01-25T13:56:36Z
dc.date.available2018-01-25T13:56:36Z
dc.date.issued2017
dc.description.abstractBACKGROUND: In most of the world, diagnostic surgery remains the most frequent approach for indeterminate thyroid cytology. Although several molecular tests are available for testing in centralized commercial laboratories in the United States, there are no available kits for local laboratory testing. The aim of this study was to develop a prototype in vitro diagnostic (IVD) gene classifier for the further characterization of nodules with an indeterminate thyroid cytology. METHODS: In a first stage, the expression of 18 genes was determined by quantitative polymerase chain reaction (qPCR) in a broad histopathological spectrum of 114 fresh-tissue biopsies. Expression data were used to train several classifiers by supervised machine learning approaches. Classifiers were tested in an independent set of 139 samples. In a second stage, the best classifier was chosen as a model to develop a multiplexed-qPCR IVD prototype assay, which was tested in a prospective multicenter cohort of fine-needle aspiration biopsies. RESULTS: In tissue biopsies, the best classifier, using only 10 genes, reached an optimal and consistent performance in the ninefold cross-validated testing set (sensitivity 93% and specificity 81%). In the multicenter cohort of fine-needle aspiration biopsy samples, the 10-gene signature, built into a multiplexed-qPCR IVD prototype, showed an area under the curve of 0.97, a positive predictive value of 78%, and a negative predictive value of 98%. By Bayes' theorem, the IVD prototype is expected to achieve a positive predictive value of 64-82% and a negative predictive value of 97-99% in patients with a cancer prevalence range of 20-40%. CONCLUSIONS: A new multiplexed-qPCR IVD prototype is reported that accurately classifies thyroid nodules and may provide a future solution suitable for local reference laboratory testing.
dc.format.extent10
dc.identifier.citationGonzález HE, Martínez JR, Vargas-Salas S, Solar A, Veliz L, Cruz F, Arias T, Loyola S, Horvath E, Tala H, Traipe E, Meneses M, Marín L, Wohllk N, Diaz RE, Véliz J, Pineda P, Arroyo P, Mena N, Bracamonte M, Miranda G, Bruce E, Urra S. A 10-Gene Classifier for Indeterminate Thyroid Nodules: Development and Multicenter Accuracy Study. Thyroid. 2017 Aug;27(8):1058-1067
dc.identifier.urihttp://hdl.handle.net/11447/1978
dc.identifier.urihttp://dx.doi.org/10.1089/thy.2017.0067
dc.language.isoen_US
dc.publisherAmerican Thyroid Association
dc.subjectgene classifier
dc.subjectin vitro diagnostic test
dc.subjectindeterminate thyroid nodules
dc.subjectqPCR
dc.titleA 10-gene classifier for indeterminate thyroid nodules: development and multicenter accuracy study
dc.typeArtículo

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