Comprehensive DNA methylation profiling identifies novel diagnostic biomarkers for thyroid cancer

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Title
Comprehensive DNA methylation profiling identifies novel diagnostic biomarkers for thyroid cancer
Author(s)
Jong Lyul Park; S Jeon; Eun Hye Seo; Dong Hyuck Bae; Y M Jeong; Y Kim; J S Bae; Seon-Kyu Kim; C K Jung; Yong Sung Kim
Bibliographic Citation
Thyroid, vol. 30, no. 2, pp. 192-203
Publication Year
2020
Abstract
Background: There are no reliable biomarkers to accurately differentiate indolent thyroid tumors from more aggressive thyroid cancers. This study aimed to develop new DNA methylation markers for diagnosis and recurrence risk stratification of papillary thyroid carcinoma (PTC). Methods: Thyroid tumor-specific DNA methylation profiling was investigated in 34 fresh frozen tissues, which included nontumor (n=7), noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP, n=6) and PTC (n=21), using the Illumina HumanMethylation EPIC array. We performed a genome-wide assessment of thyroid tumor-specific differentially methylated CpG sites in the discovery set, then validated the top candidate markers in an independent set of 293 paraffin tissue samples comprised of follicular adenoma (FA, n=61), Hurthle cell adenoma (HA, n=24), NIFTP (n=56), PTC (n=120), follicular thyroid carcinoma (n=27), and Hurthle cell carcinoma (n=5), by pyrosequencing. Results: Three selected markers (cg10705422, cg17707274, and cg26849382) differentiated nonmalignant (FA, HA, and NIFTP) tumors from differentiated thyroid cancers with area under the receiver operating characteristic curve of 0.83, 0.83, and 0.80, respectively. Low DNA methylation levels for three markers were significantly associated with recurrent or persistent disease (odds ratio (OR)=3.860 [95% confidence interval (CI) 1.194-12.475]) and distant metastasis (OR=4.009 [CI 1.098-14.632]) in patients with differentiated thyroid cancer. A subgroup analysis for the validation set showed that PTC patients with low DNA methylation levels more frequently had aggressive histology, extrathyroidal extension, lymph node metastasis, BRAFV600E mutations, and recurrent or persistent disease than those with high levels of methylation markers. All PTC patients who developed disease recurrence had low DNA methylation levels for three markers. Conclusions: DNA methylation levels of three markers can be useful for differentiating differentiated thyroid cancer from nonmalignant follicular thyroid lesions, and may serve as prognostic biomarkers for predicting recurrent or persistent disease after surgery for differentiated thyroid cancer.
Keyword
DNA methylationNIFTPmethylation markerspapillary thyroid cancerrecurrencethyroid neoplasms
ISSN
1050-7256
Publisher
Mary Ann Liebert, Inc
DOI
http://dx.doi.org/10.1089/thy.2019.0011
Type
Article
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
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