Horm Metab Res 2023; 55(12): 869-875
DOI: 10.1055/a-2188-0050
Original Article: Endocrine Research

DNA Methylation Status of HYAL1 in Malignant and Benign Thyroid Nodules

Mengxia Li
1   Department of Epidemiology and Biostatistics, Nanjing Medical University, Nanjing, China
Yifei Yin
2   Department of Thyroid and Breast Surgery, The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’an, Huai’an, China
Minmin Zhang
2   Department of Thyroid and Breast Surgery, The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’an, Huai’an, China
Chenxia Jiang
3   Department of Pathology, Nantong University Affiliated Hospital, Nantong, China
Hong Li
4   Department of Pathology, The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’an, Huai’an, China
Rongxi Yang
1   Department of Epidemiology and Biostatistics, Nanjing Medical University, Nanjing, China
› Author Affiliations


Differentiation between benign and malignant thyroid nodules has been a challenge in clinical practice. Exploring a novel biomarker to determine the malignancy of thyroid nodules has important implications. We semi-quantitatively determined the DNA methylation levels of four CpG sites located at the gene body of HYAL1 in formalin-fixed paraffin-embedded (FFPE) tissue samples from 190 early-stage papillary thyroid cancer (PTC) cases and 190 age- and gender-matched subjects with benign thyroid nodule (BTN). HYAL1 expression was evaluated by immunohistochemical (IHC) staining in another cohort of 55 PTC and 55 matched BTN cases. Covariates-adjusted odds ratios (ORs) for 10% increased methylation were calculated by binary logistic regression. A 165 bp amplicon covering four CpG sites at the second exon of HYAL1 gene was designed. After adjusted for all covariates, higher methylation level of HYAL1_CpG_3,4 in the FFPE tissue was associated with PTC (OR per 10% increased methylation=1.53, p=0.025), even with stage І PTC (OR per 10% increased methylation=1.58, p=0.021). Hypermethylation of HYAL1_CpG_3,4 had a significant association with early-stage PTC in the females (OR per 10% increased methylation=1.60, p=0.028) rather than in the males. Besides, we found the higher expression of HYAL1 protein in PTC than that in BTN patients (IHC score: 2.3 vs. 0.5, p=1.00E-06). Our study suggested altered methylation and expression of HYAL1 could be a novel and potential biomarker in distinguishing malignant and benign thyroid nodules.

Publication History

Received: 26 May 2022

Accepted after revision: 29 September 2023

Article published online:
01 December 2023

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