Detection of DNA methylation of HYAL2 gene for differentiating malignant from benign thyroid tumors.
10.12122/j.issn.1673-4254.2022.01.15
- Author:
Yi Fei YIN
1
;
Hong LI
1
;
Chun Sheng YANG
1
;
Min Min ZHANG
1
;
Xuan Dong HUANG
1
;
Meng Xia LI
2
;
Rong Xi YANG
2
;
Zheng Dong ZHANG
2
Author Information
1. Department of Thyroid and Breast Surgery, Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an 223001, China.
2. School of Public Health, Nanjing Medical University, Nanjing 211166, China.
- Publication Type:Journal Article
- Keywords:
DNA methylation;
HYAL2 gene;
differential diagnosis;
molecular marker;
thyroid tumor
- MeSH:
Adenoma, Oxyphilic/genetics*;
Biomarkers, Tumor/metabolism*;
Cell Adhesion Molecules/metabolism*;
DNA Methylation;
GPI-Linked Proteins/metabolism*;
Humans;
Hyaluronoglucosaminidase/metabolism*;
Immunohistochemistry;
Middle Aged;
Thyroid Cancer, Papillary/pathology*;
Thyroid Neoplasms/pathology*
- From:
Journal of Southern Medical University
2022;42(1):123-129
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To assess the value of DNA methylation level of HYAL2 gene as a molecular marker for differential diagnosis of malignant and benign thyroid tumors.
METHODS:DNA methylation of HYAL2 gene in tissue specimens of 190 patients with papillary thyroid cancer (PTC) and 190 age- and gender-matched patients with benign thyroid tumors was examined by mass spectrometry, and the protein expression of HYAL2 was detected immunohistochemically for another 55 pairs of patients. Logistic regression analysis was performed to calculate the odds ratio (OR) and evaluate the correlation of per 10% reduction in DNA methylation with PTC. Receiver operating characteristic (ROC) curve analysis was performed and the area under curve (AUC) was calculated to assess the predictive value of alterations in HYAL2 methylation.
RESULTS:Hypomethylation of HYAL2_CpG_3 was significantly correlated with early-stage PTC (OR=1.51, P=0.001), even in stage I cancer (OR=1.42, P=0.007). Age-stratified analysis revealed a significantly stronger correlation between increased HYAL2_CpG_ 3 methylation and early-stage PTC in patients below 50 years than in those older than 50 years (OR: 1.89 vs 1.37, P < 0.05); ROC analysis also showed a larger AUC of 0.787 in younger patients. The results of immunohistochemistry showed that patients with PTC had significantly higher protein expressions of HYAL2 than patients with benign tumors.
CONCLUSION:The alterations of DNA methylation level of HYAL2 gene is significantly correlated with early-stage PTC, suggesting the value of DNA methylation level as a potential biomarker for differentiation of malignant from benign thyroid tumors.
