High Diagnostic Accuracy of Epigenetic Imprinting Biomarkers in Thyroid Nodules
Hui‐Xiong Xu, Yifeng Zhang, Hongxun Wu, Ning Zhou, Xing Li, John Pineda, Yun Zhu, Hui‐Jun Fu, Mingsheng Ying, Shufang Yang, Jiandong Bao, Lulu Yang, Bingjie Zhang, Le‐Hang Guo, Liping Sun, Feng Lu, Hanxiang Wang, Ying Huang, Tiantong Zhu, Xiaonan Wang, Qing Wei, Chunjun Sheng, Shen Qu, Zhongwei Lv, Dong Xu, Qian Li, Yongling Dong, Jianwu Qin, Tong Cheng, Mingzhao Xing
Abstract
PURPOSE: To explore the novel diagnostic value of epigenetic imprinting biomarkers in thyroid nodules. PATIENTS AND METHODS: , on the basis of which a diagnostic grading model for thyroid nodules was developed. The model was retrospectively trained on 124 postsurgical thyroid samples, optimized on 32 presurgical FNA samples, and prospectively validated on 394 presurgical FNA samples. Blinded central review-based cytopathologic and histopathologic diagnoses were used as the reference standard. RESULTS: For thyroid malignancy, the QCIGISH test achieved an overall diagnostic sensitivity of 100% (277/277), a specificity of 91.5% (107/117; 95% CI, 86.4 to 96.5), a positive predictive value (PPV) of 96.5% (95% CI, 94.4 to 98.6), and a negative predictive value (NPV) of 100% in the prospective validation, with a diagnostic accuracy of 97.5% (384/394; 95% CI, 95.9 to 99.0). QCIGISH demonstrated a PPV of 97.8% (95% CI, 94.7 to 100) and NPV of 100%, with a diagnostic accuracy of 98.2% (111/113; 95% CI, 95.8 to 100), for indeterminate Bethesda III-V thyroid nodules. QCIGISH demonstrated a PPV of 96.6% (95% CI, 91.9 to 100) and a NPV of 100%, with a diagnostic accuracy of 97.5% (79/81; 95% CI, 94.2 to 100), for Bethesda III-IV. For Bethesda VI, QCIGISH showed a 100% (184/184) accuracy. CONCLUSION: This imprinting biomarker-based test can effectively distinguish malignant from benign thyroid nodules. The high PPV and NPV make the test both an excellent rule-in and rule-out diagnostic tool. With such a diagnostic performance and its technical simplicity, this novel thyroid molecular test is clinically widely applicable.