TY - JOUR
T1 - High Diagnostic Accuracy of Epigenetic Imprinting Biomarkers in Thyroid Nodules
AU - Xu, Huixiong
AU - Zhang, Yifeng
AU - Wu, Hongxun
AU - Zhou, Ning
AU - Li, Xing
AU - Pineda, John P.
AU - Zhu, Yun
AU - Fu, Huijun
AU - Ying, Ming
AU - Yang, Shufang
AU - Bao, Jiandong
AU - Yang, Lulu
AU - Zhang, Bingjie
AU - Guo, Lehang
AU - Sun, Liping
AU - Lu, Feng
AU - Wang, Hanxiang
AU - Huang, Ying
AU - Zhu, Tiantong
AU - Wang, Xiaonan
AU - Wei, Qing
AU - Sheng, Chunjun
AU - Qu, Shen
AU - Lv, Zhongwei
AU - Xu, Dong
AU - Li, Qian
AU - Dong, Yongling
AU - Qin, Jianwu
AU - Cheng, Tong
AU - Xing, Mingzhao
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2023/2/20
Y1 - 2023/2/20
N2 - PURPOSETo explore the novel diagnostic value of epigenetic imprinting biomarkers in thyroid nodules.PATIENTS AND METHODSA total of 550 patients with fine-needle aspiration (FNA)-evaluated and histopathologically confirmed thyroid nodules were consecutively recruited from eight medical centers. Quantitative chromogenic imprinted gene in situ hybridization (QCIGISH) was used to assess the allelic expression of imprinted genes SNRPN and HM13, 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.RESULTSFor 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.CONCLUSIONThis 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.
AB - PURPOSETo explore the novel diagnostic value of epigenetic imprinting biomarkers in thyroid nodules.PATIENTS AND METHODSA total of 550 patients with fine-needle aspiration (FNA)-evaluated and histopathologically confirmed thyroid nodules were consecutively recruited from eight medical centers. Quantitative chromogenic imprinted gene in situ hybridization (QCIGISH) was used to assess the allelic expression of imprinted genes SNRPN and HM13, 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.RESULTSFor 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.CONCLUSIONThis 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.
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U2 - 10.1200/JCO.22.00232
DO - 10.1200/JCO.22.00232
M3 - Article
C2 - 36378996
AN - SCOPUS:85146309880
SN - 0732-183X
VL - 41
SP - 1296
EP - 1306
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 6
ER -