| Popis: |
Although most thyroid nodules can be diagnosed preoperatively by thyroid ultrasonography and fine-needle aspiration biopsy, it remains a challenge to accurately identify malignancy of thyroid nodules when the biopsy is indeterminate. This study aims to explore a novel biomarker to distinguish benign and malignant thyroid nodules. Tissue samples from patients with Stage I&II papillary thyroid carcinoma (PTC) and benign thyroid nodules (BTN) were collected for genome profiling by methylation EPIC 850K array and RNA-Sequencing. Genes with significantly differential DNA methylation and inverse mRNA expression were filtered out. The altered methylation ofRUNX1gene was validated in two independent case-control studies with a total of 699 formalin fixed paraffin-embedded (FFPE) samples using mass spectrometry and calculated by binary logistic regression analysis. Hypomethylation ofRUNX1gene in PTC patients compared to BTN subjects was verified in Validation Ⅰ (140 PTC vs. 189 BTN, ORs ≥ 1.50 per-10% methylation,P≤ 4.40E-05, for all measurable CpG sites) and Validation Ⅱ (184 PTC vs. 186 BTN, ORs ≥ 1.72 per-10% methylation,P≤ 2.38E-11, for all measurable CpG sites). Besides,RUNX1methylation achieved good accuracy in differentiating early-stage PTC from BTN in Validation Ⅰ (AUC: 0.74) and Validation Ⅱ (AUC: 0.79). Gender- and age-stratified analysis revealedRUNX1hypomethylation as an important risk factor for thyroid disease in younger women. We disclosed a significant association betweenRUNX1hypomethylation and PTC, suggestingRUNX1methylation based on FFPE tissue samples as a potential biomarker for predicting malignancy of thyroid nodules. |
