Identification of new biomarkers for human papillary thyroid carcinoma employing NanoString analysis
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Zhanna Chitikova1, Marc Pusztaszeri2, Anne-Marie Makhlouf1, Margaret Berczy2, Celine Delucinge-Vivier3, Frederic Triponez4, Patrick Meyer5, Jacques Philippe1,5, Charna Dibner1,5
1Department of Medical Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland
2Division of Clinical Pathology, University Hospital of Geneva, Switzerland
3iGE3Genomics Platform, University of Geneva, Switzerland
4Department of Thoracic and Endocrine Surgery, University Hospital of Geneva, Geneva, Switzerland
5Division of Endocrinology, Diabetes, Hypertension and Nutrition, University Hospital of Geneva, Geneva, Switzerland
Charna Dibner, e-mail: [email protected]
Keywords: papillary thyroid carcinoma, NanoString analysis, FFPE, biomarkers, circadian clock
Received: January 22, 2015 Accepted: February 25, 2015 Published: March 26, 2015
We previously reported an upregulation of the clock transcript BMAL1, correlating with TIMP1 expression in fresh-frozen samples from papillary thyroid carcinoma (PTC). Since frozen postoperative biopsy samples are difficult to obtain, we aimed to validate the application of high-precision NanoString analysis for formalin-fixed paraffin-embedded (FFPE) thyroid nodule samples and to screen for potential biomarkers associated with PTC. No significant differences were detected between fresh-frozen and FFPE samples. NanoString analysis of 51 transcripts in 17 PTC and 17 benign nodule samples obtained from different donors and in 24 pairs of benign and PTC nodules, obtained from the same donor (multinodular goiters), confirmed significant alterations in the levels of BMAL1, c-MET, c-KIT, TIMP1, and other transcripts. Moreover, we identified for the first time alterations in CHEK1 and BCL2 levels in PTC. A predictive score was established for each sample, based on the combined expression levels of BMAL1, CHEK1, c-MET, c-KIT and TIMP1. In combination with BRAF mutation analysis, this predictive score closely correlated with the clinicopathological characteristics of the analyzed thyroid nodules. Our study identified new thyroid transcripts with altered levels in PTC using the NanoString approach. A predictive score correlation coefficient might contribute to improve the preoperative diagnosis of thyroid nodules.
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