Oncotarget

Research Papers:

Identification of new biomarkers for human papillary thyroid carcinoma employing NanoString analysis

Zhanna Chitikova, Marc Pusztaszeri, Anne-Marie Makhlouf, Margaret Berczy, Celine Delucinge-Vivier, Frederic Triponez, Patrick Meyer, Jacques Philippe and Charna Dibner _

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Oncotarget. 2015; 6:10978-10993. https://doi.org/10.18632/oncotarget.3452

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Abstract

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

Correspondence to:

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

ABSTRACT

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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