Yin Y, Li H, Yang C, Zhang M, Huang X, Li M, Yang R, Zhang Z
Department of Thyroid and Breast Surgery, Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an 223001, China.
School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2022 Jan 20;42(1):123-129. doi: 10.12122/j.issn.1673-4254.2022.01.15.
To assess the value of DNA methylation level of gene as a molecular marker for differential diagnosis of malignant and benign thyroid tumors.
DNA methylation of 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 methylation.
Hypomethylation of _CpG_3 was significantly correlated with early-stage PTC (OR=1.51, =0.001), even in stage I cancer (OR=1.42, =0.007). Age-stratified analysis revealed a significantly stronger correlation between increased CpG 3 methylation and early-stage PTC in patients below 50 years than in those older than 50 years (OR: 1.89 1.37, < 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.
The alterations of DNA methylation level of 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.
评估基因的DNA甲基化水平作为甲状腺良恶性肿瘤鉴别诊断分子标志物的价值。
采用质谱法检测190例甲状腺乳头状癌（PTC）患者及190例年龄、性别匹配的甲状腺良性肿瘤患者组织标本中基因的DNA甲基化情况，另对55对患者进行免疫组织化学检测HYAL2蛋白表达。进行逻辑回归分析计算比值比（OR），评估DNA甲基化每降低10%与PTC的相关性。绘制受试者工作特征（ROC）曲线并计算曲线下面积（AUC），以评估甲基化改变的预测价值。
CpG_3低甲基化与早期PTC显著相关（OR=1.51，=0.001），即使在I期癌症中也是如此（OR=1.42，=0.007）。年龄分层分析显示，50岁以下患者中_CpG 3甲基化增加与早期PTC的相关性明显强于50岁以上患者（OR：1.89对1.37，<0.05）；ROC分析还显示年轻患者的AUC更大，为0.787。免疫组织化学结果显示，PTC患者的HYAL2蛋白表达明显高于良性肿瘤患者。
基因DNA甲基化水平的改变与早期PTC显著相关，提示DNA甲基化水平作为甲状腺良恶性肿瘤鉴别的潜在生物标志物具有一定价值。
