Construction and validation of BRAF mutation diagnostic model based on ultrasound examination and clinical features of patients with thyroid nodules

Chan Xu; Jianqiang Fang; Wanying Li; Chenyu Sun; Yaru Li; Scott Lowe; Rachel Bentley; Shuya Chen; Cunyu He; Xinxin Li; Bing Wang; Chengliang Yin; Wenxian Li; Wenle Li

doi:10.3389/fgene.2022.973272

Construction and validation of BRAF mutation diagnostic model based on ultrasound examination and clinical features of patients with thyroid nodules

Front Genet. 2022 Sep 8:13:973272. doi: 10.3389/fgene.2022.973272. eCollection 2022.

Authors

Chan Xu^{1

2}, Jianqiang Fang^{2

3}, Wanying Li², Chenyu Sun⁴, Yaru Li⁵, Scott Lowe⁶, Rachel Bentley⁶, Shuya Chen⁷, Cunyu He², Xinxin Li², Bing Wang², Chengliang Yin⁸, Wenxian Li⁹, Wenle Li^{2

10

11}

Affiliations

¹ Department of Dermatology, Xianyang Central Hospital, Xianyang, China.
² Clinical Medical Research Center, Xianyang Central Hospital, Xianyang, China.
³ Department of Ultrasound Interventional, Xianyang Central Hospital, Xianyang, China.
⁴ AMITA Health Saint Joseph Hospital Chicago, Chicago, IL, United States.
⁵ Internal Medicine, Swedish Hospital, Chicago, IL, United States.
⁶ College of Osteopathic Medicine, Kansas City University, Kansas City, MO, United States.
⁷ Newham University Hospital, London, United Kingdom.
⁸ Faculty of Medicine, Macau University of Science and Technology, Macau, China.
⁹ Beijing Life Biosciences Co., LTD, Beijing, China.
¹⁰ Department of Orthopaedics II, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
¹¹ Center for Molecular Imaging and Translational Medicine, Xiamen University, Xiamen, China.

Abstract

Introduction: Fine Needle Aspiration (FNA) is currently the most popular method for identifying benign and malignant thyroid nodules. However, its diagnostic sensitivity is sometimes limited, which makes it necessary to apply genetic testing and other modalities as a secondary diagnostic method. The diagnostic accuracy of thyroid nodule can be improved by combining mutations in the B-Raf proto-oncogene serine/threonine kinase (BRAF) with FNA. Thus, this study was conducted to create a nomogram diagnostic model based on the clinical and ultrasonic characteristics of patients with BRAF mutations to aid in the identification of benign and malignant thyroid nodules using FNA. Methods: From April 2018 to December 2021, 275 patients with thyroid nodules who underwent ultrasonography and BRAF gene testing (137 positive and 138 negative) were included from Xianyang Central Hospital. The clinical and ultrasonic characteristics of the patients were used to develop a nomographic, diagnostic model of BRAF gene mutation, and to validate and evaluate the usefulness of the model. Results: Independent risk factors for BRAF mutations included: focal strong echogenicity (microcalcifications, OR = 3.04, 95%CI = 1.41-6.58, p = 0.005), hypoechogenicity (OR = 3.8, 95%CI = 1.14-12.61, p = 0.029), lymph node metastases (OR = 3.54, 95%CI = 1.43-8.75, p = 0.006), margin (lobulated, OR = 3.7, 95%CI = 1.66-8.23, p = 0.001; extrathyroidal invasion, OR = 2.81, 95%CI = 1.11-7.06, p = 0.029), and shape (vertical position, OR = 2.7, 95%CI = 1.11-6.59, p = 0.029). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the BRAF mutation diagnostic model constructed on these factors was 0.806 (95% CI = 0.754-0.851), and 39.5% was set as the threshold probability of making a clinical decision. The results of the validation and clinical utility evaluation showed that our model had good predictive performance and clinical application value. Conclusion: Our nomogram diagnostic model based on clinical and ultrasound features of patients accurately predicted the possibility of BRAF gene mutations in patients with thyroid nodules.

Keywords: BRAF gene; nomogram; prediction model; thyroid nodule; ultrasonography.