High Diagnostic Accuracy of Epigenetic Imprinting Biomarkers in Thyroid Nodules

Xu，Huixiong1,2,3; Zhang，Yifeng1,2; Wu，Hongxun4; Zhou，Ning5; Li，Xing5; Pineda，John P.5; Zhu，Yun4; Fu，Huijun2,6; Ying，Ming7; Yang，Shufang7,8; Bao，Jiandong4; Yang，Lulu9; Zhang，Bingjie4; Guo，Lehang1,2; Sun，Liping1,2; Lu，Feng1,2; Wang，Hanxiang1,2; Huang，Ying10; Zhu，Tiantong10; Wang，Xiaonan5; Wei，Qing2,11; Sheng，Chunjun2,11; Qu，Shen2,12; Lv，Zhongwei2; Xu，Dong13; Li，Qian14; Dong，Yongling14; Qin，Jianwu15; Cheng，Tong5; Xing，Mingzhao16

2023-02-20

10.1200/JCO.22.00232

JOURNAL OF CLINICAL ONCOLOGY   影响因子和分区

0732-183X

1527-7755

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.

SCI

英语

NI论文

通讯

Oncology

Oncology

WOS:000970386000017

LIPPINCOTT WILLIAMS & WILKINS

CLINICAL MEDICINE

2-s2.0-85146309880

Scopus

1.Department of Medical Ultrasound,Shanghai Tenth People's Hospital,Ultrasound Research and Education Institute,Tongji University Cancer Center,Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment,School of Medicine,Tongji University,Shanghai,China
2.The Thyroid Research Center of Shanghai,Shanghai Tenth People's Hospital,School of Medicine,Tongji University,Shanghai,China
3.Department of Ultrasound,Zhongshan Hospital,Fudan University,Shanghai,China
4.Departments of Endocrinology,Ultrasound and Pathology,JiangYuan Hospital Affiliated to Jiangsu Institute of Nuclear Medicine,Wuxi,Jiangsu,China
5.Lisen Imprinting Diagnostics Inc,Wuxi,Jiangsu,China
6.Department of Pathology,Shanghai Tenth People's Hospital,School of Medicine,Tongji University,Shanghai,China
7.Departments of Ultrasound and Endocrinology,Taizhou People's Hospital,Taizhou,Jiangsu,China
8.Department of Endocrinology,Taizhou Third People's Hospital,Taizhou,Jiangsu,China
9.Department of Pathology,Nanjing First Hospital,Nanjing,Jiangsu,China
10.Department of Ultrasound,Shengjing Hospital,China Medical University,Shenyang,Liaoning,China
11.Department of Endocrinology and Metabolism,Shanghai Tenth People's Hospital,School of Medicine,Tongji University,Shanghai,China
12.Department of Nuclear Medicine,Shanghai Tenth People's Hospital,School of Medicine,Tongji University,Shanghai,China
13.Department of Ultrasound,Cancer Hospital of the University,Chinese Academy of Sciences,Hangzhou,Zhejiang,China
14.Department of Ultrasound,Henan Cancer Hospital,Zhengzhou,Henan,China
15.Department of Thyroid and Breast Surgery,Henan Cancer Hospital,Zhengzhou,Henan,China
16.School of Medicine,Southern University of Science and Technology,Shenzhen,Guangdong,China

Xu，Huixiong,Zhang，Yifeng,Wu，Hongxun,et al. High Diagnostic Accuracy of Epigenetic Imprinting Biomarkers in Thyroid Nodules[J]. JOURNAL OF CLINICAL ONCOLOGY,2023,41(6):1296-1306.

Xu，Huixiong.,Zhang，Yifeng.,Wu，Hongxun.,Zhou，Ning.,Li，Xing.,...&Xing，Mingzhao.(2023).High Diagnostic Accuracy of Epigenetic Imprinting Biomarkers in Thyroid Nodules.JOURNAL OF CLINICAL ONCOLOGY,41(6),1296-1306.

Xu，Huixiong,et al."High Diagnostic Accuracy of Epigenetic Imprinting Biomarkers in Thyroid Nodules".JOURNAL OF CLINICAL ONCOLOGY 41.6(2023):1296-1306.