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

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

Thyroid. 2017 May 18;:

Authors: Gonzalez HE, Martínez JR, Vargas S, Solar A, Véliz LP, Cruz F, Arias T, Loyola S, Horvath E, Tala H, Traipe E, Meneses M, Marin L, Wohllk N, Diaz RE, Véliz J, Pineda P, Arroyo P, Mena N, Bracamonte M, Miranda G, Bruce E, Urra S

Abstract
BACKGROUND: In most of the world, diagnostic surgery remains as the most frequent approach for indeterminate thyroid cytology. Although several molecular tests are available for central-lab testing in the US, 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 diagnosis of indeterminate thyroid cytology.
METHODS: In a first stage, the expression of 18 genes was determined by qPCR in a broad histopathological spectrum of fresh tissue biopsies (114). Expression data was 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 (FNA) biopsies.
RESULTS: In tissue biopsies, the best classifier, using only 10 genes, reached an optimal and consistent performance in the 9-fold cross-validated testing set (sensitivity 93% and specificity 81%). In the multicenter cohort of FNA samples, the 10-gene signature, built into a multiplexed-qPCR IVD prototype showed an area under the curve of 0.96, a positive predictive value (PPV) of 87% and a negative predictive value (NPV) of 98%. By Bayes theorem, the IVD prototype is expected to achieve a PPV of 78%-90% and a NPV of 96%-99% in patients with a cancer prevalence range of 20%-40%.
CONCLUSIONS: We report a new multiplexed-qPCR IVD prototype that accurately classifies thyroid nodules and may provide a future solution suitable for expanded local reference laboratory testing.

PMID: 28521616 [PubMed - as supplied by publisher]

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