Oncotarget

Research Papers:

Identification of CHEK1, SLC26A4, c-KIT, TPO and TG as new biomarkers for human follicular thyroid carcinoma

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

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Oncotarget. 2016; 7:45776-45788. https://doi.org/10.18632/oncotarget.10166

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Abstract

Anne-Marie Makhlouf1,*, Zhanna Chitikova1,*, Marc Pusztaszeri2, 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, Geneva, Switzerland

3iGE3 Genomics Platform, University of Geneva, 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

*These authors contributed equally to this work

Correspondence to:

Charna Dibner, email: Charna.Dibner@hcuge.ch

Keywords: follicular thyroid carcinoma, poorly differentiated thyroid carcinoma, NanoString analysis, diagnostic biomarkers

Received: April 01, 2016     Accepted: June 03, 2016     Published: June 18, 2016

ABSTRACT

The search for preoperative biomarkers for thyroid malignancies, in particular for follicular thyroid carcinoma (FTC) diagnostics, is of utmost clinical importance. We thus aimed at screening for potential biomarker candidates for FTC. To evaluate dynamic alterations in molecular patterns as a function of thyroid malignancy progression, a comparative analysis was conducted in clinically distinct subgroups of FTC and poorly differentiated thyroid carcinoma (PDTC) nodules. NanoString analysis of FFPE samples was performed in 22 follicular adenomas, 56 FTC and 25 PDTC nodules, including oncocytic and non-oncocytic subgroups. The expression levels of CHEK1, c-KIT, SLC26A4, TG and TPO were significantly altered in all types of thyroid carcinomas. Based on collective changes of these biomarkers which correlating among each other, a predictive score has been established, allowing for discrimination between benign and FTC samples with high sensitivity and specificity. Additional transcripts related to thyroid function, cell cycle, circadian clock, and apoptosis regulation were altered in the more aggressive oncocytic subgroups only, with expression levels correlating with disease progression. Distinct molecular patterns were observed for oncocytic and non-oncocytic FTCs and PDTCs. A predictive score correlation coefficient based on collective alterations of identified here biomarkers might help to improve the preoperative diagnosis of FTC nodules.


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