Identification of DNA methylation signatures in follicular-patterned thyroid tumors

Truong Phan-Xuan Nguyen; Hoang Minh Nguyen; Loi Phuc Luu; Dat Quoc Ngo; Shanop Shuangshoti; Nakarin Kitkumthorn; Somboon Keelawat

doi:10.1016/j.prp.2024.155794

Identification of DNA methylation signatures in follicular-patterned thyroid tumors

Pathol Res Pract. 2024 Dec 31:266:155794. doi: 10.1016/j.prp.2024.155794. Online ahead of print.

Authors

Truong Phan-Xuan Nguyen¹, Hoang Minh Nguyen², Loi Phuc Luu³, Dat Quoc Ngo⁴, Shanop Shuangshoti⁵, Nakarin Kitkumthorn⁶, Somboon Keelawat⁷

Affiliations

¹ Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; Department of Pathology, Faculty of Medicine, University of Medicine & Pharmacy HCMC, Ho Chi Minh City 70000, Vietnam. Electronic address: truongxuan100492@gmail.com.
² Faculty of Biological Sciences, Nong Lam University Ho Chi Minh City, Ho Chi Minh City 70000, Vietnam. Electronic address: hoangnguyencnsh@gmail.com.
³ Institute for Applied Research in Health Sciences and Aging (ARiHA), Thong Nhat Hospital, Ho Chi Minh City 70000, Vietnam. Electronic address: luu.p.loi@googlemail.com.
⁴ Department of Pathology, Faculty of Medicine, University of Medicine & Pharmacy HCMC, Ho Chi Minh City 70000, Vietnam. Electronic address: ngoquocdat@ump.edu.vn.
⁵ Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; Chulalongkorn GenePRO Center, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. Electronic address: shanop@gmail.com.
⁶ Department of Oral Biology, Faculty of Dentistry, Mahidol University, Bangkok 10330, Thailand. Electronic address: nakarinkit@gmail.com.
⁷ Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; Precision Pathology of Neoplasia Research Group, Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. Electronic address: trcskl@gmail.com.

PMID: 39764946
DOI: 10.1016/j.prp.2024.155794

Abstract

Background and aims: Follicular-patterned thyroid tumors (FPTTs) are frequently encountered in thyroid pathology, encompassing follicular adenoma (FA), follicular thyroid carcinoma (FTC), noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), and follicular variant of papillary thyroid carcinoma (fvPTC). Recently, a distinct entity termed differentiated high-grade thyroid carcinoma has been described by the 5th edition of the WHO classification of the thyroid tumors, categorized as either high-grade fvPTC, high-grade FTC or high-grade oncocytic carcinoma of the thyroid (OCA). Accurate differentiation among these lesions, particular between the benign (FA), borderline (NIFTP) and malignant neoplasms (FTC and fvPTC), remains a challenge in both histopathological and cytological diagnoses. This study aimed to develop a novel molecular diagnostic approach utilizing DNA methylation to distinguish between these thyroid tumors.

Materials and methods: DNA methylation signatures and machine learning were employed to construct classification models for FPTTs. A total of 178 thyroid samples from the Gene Expression Omnibus were analyzed. The models were validated using two independent cohorts.

Results: 13 cytosine-guanine dinucleotides (CpGs) exhibited significant differences in methylation levels among FA, FTC, NIFTP and fvPTC. Notably, NIFTP showed hypomethylation compared to other subtypes. A Random Forest classifier, based on the methylation status of these 13 CpGs, effectively categorized the four tumor subtypes (AUC = 0.86, accuracy = 0.70 for internal data, and AUC approximately 0.80 for validation data). The selected CpGs were significantly associated with the tumor progression pathway.

Conclusion: This study established a robust method for categorizing FPTTs based on DNA methylation patterns. The identified DNA methylation approach holds clinical promise for efficiently diagnosing thyroid neoplasms.

Keywords: Bioinformatics; Borderline thyroid tumor; DNA methylation; Follicular-patterned thyroid tumors; Thyroid carcinoma.