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Comprehensive microRNA expression profiling identifies novel markers in follicular variant of papillary thyroid carcinoma


Dettmer, Matthias Stephan; Perren, Aurel; Moch, Holger; Komminoth, Paul; Nikiforov, Yuri E; Nikiforova, Marina N (2013). Comprehensive microRNA expression profiling identifies novel markers in follicular variant of papillary thyroid carcinoma. Thyroid, 23(11):1383-1389.

Abstract

Background: Follicular variant of papillary thyroid carcinoma (FVPTC) shares features of papillary (PTC) and follicular (FTC) thyroid carcinomas on a clinical, morphological, and genetic level. MiRNA deregulation was extensively studied in PTCs and FTCs; however, very limited information is available for FVPTC. The aim of this study was to assess miRNA expression in FVPTC with the most comprehensive miRNA array panel and correlate it with the clinicopathological data. Methods: Forty-four papillary thyroid carcinomas (17 FVPTC, 27 classic PTC) and 8 normal thyroid tissue samples were analyzed for expression of 748 miRNAs using Human Microarray Assays on ABI 7900 (Life Technologies). In addition, an independent set of 61 tumor and normal samples was studied for expression of novel miRNA markers detected in this study. Results: Overall, the miRNA expression profile demonstrated similar trends in expression between FVPTC and classic PTC. Fourteen miRNAs were deregulated in FVPTC with a fold change of more than 5 (up/down) including miRNAs known to be upregulated in PTC (miR-146b-3p, -146-5p, -221, -222 and miR-222-5p) and novel miRNAs (miR-375, -551b, 181-2-3p, 99b-3p). However, the levels of miRNA expression were different between these tumor types and some miRNAs were uniquely dysregulated in FVPTC allowing separation of these tumors on the unsupervised hierarchical clustering analysis. Upregulation of novel miR-375 was confirmed in a large independent set of follicular cell derived neoplasms and benign nodules and demonstrated specific upregulation for PTC. Two miRNAs (miR-181a-2-3p, miR-99b-3p) were associated with an adverse outcome in FVPTC patients by a Kaplan Meier (p<0.05) and multivariate Cox regression analysis (p<0.05). Conclusions: Despite high similarity in miRNA expression between FVPTC and classic PTC, several miRNAs were uniquely expressed in each tumor type supporting their histopathologic differences. Highly upregulated miRNA identified in this study (miR-375) can serve as a novel marker of papillary thyroid carcinoma and miR-181a-2-3p and miR-99b-3p can predict relapse free survival in patients with FVPTC potentially providing important diagnostic and predictive value.

Abstract

Background: Follicular variant of papillary thyroid carcinoma (FVPTC) shares features of papillary (PTC) and follicular (FTC) thyroid carcinomas on a clinical, morphological, and genetic level. MiRNA deregulation was extensively studied in PTCs and FTCs; however, very limited information is available for FVPTC. The aim of this study was to assess miRNA expression in FVPTC with the most comprehensive miRNA array panel and correlate it with the clinicopathological data. Methods: Forty-four papillary thyroid carcinomas (17 FVPTC, 27 classic PTC) and 8 normal thyroid tissue samples were analyzed for expression of 748 miRNAs using Human Microarray Assays on ABI 7900 (Life Technologies). In addition, an independent set of 61 tumor and normal samples was studied for expression of novel miRNA markers detected in this study. Results: Overall, the miRNA expression profile demonstrated similar trends in expression between FVPTC and classic PTC. Fourteen miRNAs were deregulated in FVPTC with a fold change of more than 5 (up/down) including miRNAs known to be upregulated in PTC (miR-146b-3p, -146-5p, -221, -222 and miR-222-5p) and novel miRNAs (miR-375, -551b, 181-2-3p, 99b-3p). However, the levels of miRNA expression were different between these tumor types and some miRNAs were uniquely dysregulated in FVPTC allowing separation of these tumors on the unsupervised hierarchical clustering analysis. Upregulation of novel miR-375 was confirmed in a large independent set of follicular cell derived neoplasms and benign nodules and demonstrated specific upregulation for PTC. Two miRNAs (miR-181a-2-3p, miR-99b-3p) were associated with an adverse outcome in FVPTC patients by a Kaplan Meier (p<0.05) and multivariate Cox regression analysis (p<0.05). Conclusions: Despite high similarity in miRNA expression between FVPTC and classic PTC, several miRNAs were uniquely expressed in each tumor type supporting their histopathologic differences. Highly upregulated miRNA identified in this study (miR-375) can serve as a novel marker of papillary thyroid carcinoma and miR-181a-2-3p and miR-99b-3p can predict relapse free survival in patients with FVPTC potentially providing important diagnostic and predictive value.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Surgical Pathology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2013
Deposited On:15 Mar 2013 09:59
Last Modified:05 Apr 2016 16:40
Publisher:Mary Ann Liebert
ISSN:1050-7256
Additional Information:This is a copy of an article published in Thyroid © 2013 copyright Mary Ann Liebert, Inc.; Thyroid is available online at: http://www.liebertonline.com.
Publisher DOI:https://doi.org/10.1089/thy.2012.0632
PubMed ID:23427895

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