<b><i>RUNX1</i></b><b> Methylation as a Cancer Biomarker in Differentiating Papillary </b><b>Thyroid Carcinoma from Benign Thyroid Nodules</b>

<b>Aim:</b> It remains a challenge to accurately identify malignancy of thyroid nodule when biopsy is indeterminate. We aimed to investigate the abnormal DNA methylation signatures in papillary thyroid carcinoma (PTC) compared to benign thyroid nodule (BTN). <b>Methods:</b> We performed genome profiling by 850K array and RNA-Sequencing in early-stage PTC and BTN tissue samples. The identified gene was validated in two independent case-control studies using mass spectrometry. <b>Results:</b> Hypomethylation of RUNX1 in PTC was identified and verified (all ORs ≥ 1.50). RUNX1 methylation achieved good accuracy in differentiating early-stage PTC from BTN, especially for younger women. <b>Conclusion</b><b>s</b><b>:</b> We disclosed a significant association between RUNX1 hypomethylation and PTC, suggesting RUNX1 methylation as a potential biomarker for companion diagnosis of malignant thyroid nodules.