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.
Highlights
Thyroid carcinomas are the most common type of endocrine malignancies, with an incidence steadily increasing worldwide [1]
The expression levels of Checkpoint Kinase 1 (CHEK1), V-Kit Hardy-Zuckerman Feline Sarcoma (c-KIT), Solute Carrier Family 26 (SLC26A4), TG and thyroid peroxidase (TPO) were significantly altered in all types of thyroid carcinomas
NanoString analysis revealed that transcriptional pattern of the benign thyroid nodule was not significantly altered for any of 22 analyzed genes, in comparison to healthy thyroid tissue, with no transcript exhibiting significant difference in their false discovery rate (FDR) 5% (Supplementary Table S5)
Summary
Thyroid carcinomas are the most common type of endocrine malignancies, with an incidence steadily increasing worldwide [1]. The classification of thyroid carcinomas is made according to cell origin, with welldifferentiated thyroid carcinomas (papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC)) being the most frequent types. Fine-needle aspiration (FNA) biopsy is the standard diagnostic test recommended for the clinical evaluation of thyroid non-secreting nodules ≥ 1 cm [3]. While FNA allows for the reliable recognition of most classical PTC cases, it stays indeterminate in about 20–30% of cases, mostly for malignant follicular lesions. The differentiation between benign follicular adenoma and FTC is virtually impossible based on cytological features, since the hallmark of malignancy in FTC is the presence of capsular or vascular invasion, which cannot be assessed www.impactjournals.com/oncotarget by FNA. The majority of indeterminate cases are classified as benign, revealing a significant rate of unnecessary surgeries, complications, and even morbidity [1]
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