Can mutation abundance assess the biological behavior of BRAF V600E-positive papillary thyroid carcinoma?
Abstract Background BRAF V600E mutation is the most common genetic change in papillary thyroid carcinoma (PTC). Nevertheless, the association between BRAF V600E mutation status and abundance and the biological behavior of PTC is unclear. Thus, this study investigated whether BRAF V600E mutation stat...
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2025-07-01
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| author | Yeqin Ni Ping Song Xiangfeng Lin Jingjing Shi Qian Shi Yuanhui Li Siyu Zhu Tianhan Zhou Yanping Xun Shirong Zhang Xingchang Ren Kaining Lu Fan Wu Wei Wang Pan Zhao Rongjing Zhou Wenhua Zhang Dandan Li Jiaoping Zhang Chuanghua Chen Linlin Mao Li Zhou Gang Pan You Peng Yunxian Yu Yuying Chen Rong Ni Guhan Luo Yu Zhang Jugao Fang Haitao Zheng Dingcun Luo |
| author_facet | Yeqin Ni Ping Song Xiangfeng Lin Jingjing Shi Qian Shi Yuanhui Li Siyu Zhu Tianhan Zhou Yanping Xun Shirong Zhang Xingchang Ren Kaining Lu Fan Wu Wei Wang Pan Zhao Rongjing Zhou Wenhua Zhang Dandan Li Jiaoping Zhang Chuanghua Chen Linlin Mao Li Zhou Gang Pan You Peng Yunxian Yu Yuying Chen Rong Ni Guhan Luo Yu Zhang Jugao Fang Haitao Zheng Dingcun Luo |
| author_sort | Yeqin Ni |
| collection | DOAJ |
| description | Abstract Background BRAF V600E mutation is the most common genetic change in papillary thyroid carcinoma (PTC). Nevertheless, the association between BRAF V600E mutation status and abundance and the biological behavior of PTC is unclear. Thus, this study investigated whether BRAF V600E mutation status and abundance are related to PTC biological behavior and whether BRAF V600E mutation abundance can be used to further stratify risk. Methods Postoperative formalin-fixed paraffin-embedded (FFPE) specimens from 528 PTC patients formed the retrospective cohort, and preoperative fine-needle aspiration (FNA) specimens from 167 PTC patients formed the prospective cohort. Furthermore, 74 FNA specimens were collected from two additional hospitals to form the external cohort. Droplet digital polymerase chain reaction (ddPCR) was used to detect BRAF V600E mutation status and abundance in the two types of specimens. The relationship between BRAF V600E mutation status and abundance and PTC biological behavior was analyzed in the cohorts. To predict BRAF V600E-positive PTC risk stratification, we constructed postoperative clinicopathological models (Model A, retrospective; Model B, prospective), a preoperative clinical model (Model C), and a fusion model combining BRAF V600E mutation abundance and preoperative clinical information (Model D). The area under the curve (AUC) values were used to assess the performance of these models. Results Univariate and multivariate analysis of the retrospective, prospective and external cohorts indicated that BRAF V600E mutation abundance, not status, was significantly associated with PTC biological behavior. An increase in BRAF V600E mutation abundance was significantly associated with an increased risk of BRAF V600E-positive PTC. The AUCs of model A, model B, model C, and model D in the validation sets were 0.89 (95% CI, 0.83–0.94), 0.89 (95% CI, 0.83–0.99), 0.65 (95% CI, 0.48–0.82), and 0.86 (95% CI, 0.75–0.98), respectively. The AUCs of model B, model C, and model D in the external sets were 0.78(95% CI, 0.67–0.88), 0.61(95% CI, 0.48–0.75) and 0.82 (95% CI, 0.71–0.93), respectively. The AUC of model D was higher than that of model C in the external validation set by 21% (P = 0.02). Conclusions BRAF V600E mutation abundance, not status, reflects PTC biological behavior. Integrating BRAF V600E mutation abundance and preoperative clinical information can be used to better preoperatively predict BRAF V600E-positive PTC risk and guide clinical decision making. Trial registration ChiCTR, ChiCTR2300071472. Registered 31 July 2016 - Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=190478 . |
| format | Article |
| id | doaj-art-d5ce1bb07efa4c319ea030b892404b7c |
| institution | DOAJ |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | Journal of Translational Medicine |
| spelling | doaj-art-d5ce1bb07efa4c319ea030b892404b7c2025-08-20T03:04:10ZengBMCJournal of Translational Medicine1479-58762025-07-0123111310.1186/s12967-025-06493-4Can mutation abundance assess the biological behavior of BRAF V600E-positive papillary thyroid carcinoma?Yeqin Ni0Ping Song1Xiangfeng Lin2Jingjing Shi3Qian Shi4Yuanhui Li5Siyu Zhu6Tianhan Zhou7Yanping Xun8Shirong Zhang9Xingchang Ren10Kaining Lu11Fan Wu12Wei Wang13Pan Zhao14Rongjing Zhou15Wenhua Zhang16Dandan Li17Jiaoping Zhang18Chuanghua Chen19Linlin Mao20Li Zhou21Gang Pan22You Peng23Yunxian Yu24Yuying Chen25Rong Ni26Guhan Luo27Yu Zhang28Jugao Fang29Haitao Zheng30Dingcun Luo31Department of Surgical Oncology, Affiliated Hangzhou First People’s Hospital, Westlake University School of MedicineDepartment of Surgical Oncology, Affiliated Hangzhou First People’s Hospital, Westlake University School of MedicineDepartment of Thyroid Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao UniversityDepartment of Surgical Oncology, Affiliated Hangzhou First People’s Hospital, Westlake University School of MedicineDepartment of Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical UniversityDepartment of Surgical Oncology, Affiliated Hangzhou First People’s Hospital, Westlake University School of MedicineDepartment of Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical UniversityDepartment of General Surgery, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical UniversityCentre of Translational Medicine, Affiliated Hangzhou First People’s Hospital, Westlake University School of MedicineCentre of Translational Medicine, Affiliated Hangzhou First People’s Hospital, Westlake University School of MedicineDepartment of Pathology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical UniversityDepartment of Breast Surgery, the First Affiliated Hospital of Nanjing Medical UniversityDepartment of Surgical Oncology, Affiliated Hangzhou First People’s Hospital, Westlake University School of MedicineDepartment of Pathology, Affiliated Hangzhou First People’s Hospital, Westlake University School of MedicineDepartment of Pathology, Affiliated Hangzhou First People’s Hospital, Westlake University School of MedicineDepartment of Pathology, Affiliated Hangzhou Cancer Hospital, Zhejiang University School of MedicineDepartment of Pathology, Affiliated Hangzhou First People’s Hospital, Westlake University School of MedicineDepartment of Pathology, Affiliated Hangzhou First People’s Hospital, Westlake University School of MedicineDepartment of Surgical Oncology, Affiliated Hangzhou First People’s Hospital, Westlake University School of MedicineDepartment of Ultrasonography, Affiliated Hangzhou First People’s Hospital, Westlake University School of MedicineDepartment of Surgical Oncology, Affiliated Hangzhou First People’s Hospital, Westlake University School of MedicineDepartment of Surgical Oncology, Affiliated Hangzhou First People’s Hospital, Westlake University School of MedicineDepartment of Surgical Oncology, Affiliated Hangzhou First People’s Hospital, Westlake University School of MedicineDepartment of Surgical Oncology, Affiliated Hangzhou First People’s Hospital, Westlake University School of MedicineDepartment of Epidemiology & biostatistics, School of Public Health, Zhejiang UniversityThe Fourth School of Clinical Medicine, Zhejiang Chinese Medical UniversityThe Fourth School of Clinical Medicine, Zhejiang Chinese Medical UniversityThe Fourth School of Clinical Medicine, Zhejiang Chinese Medical UniversityDepartment of Surgical Oncology, Affiliated Hangzhou First People’s Hospital, Westlake University School of MedicineDepartment of Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical UniversityDepartment of Thyroid Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao UniversityDepartment of Surgical Oncology, Affiliated Hangzhou First People’s Hospital, Westlake University School of MedicineAbstract Background BRAF V600E mutation is the most common genetic change in papillary thyroid carcinoma (PTC). Nevertheless, the association between BRAF V600E mutation status and abundance and the biological behavior of PTC is unclear. Thus, this study investigated whether BRAF V600E mutation status and abundance are related to PTC biological behavior and whether BRAF V600E mutation abundance can be used to further stratify risk. Methods Postoperative formalin-fixed paraffin-embedded (FFPE) specimens from 528 PTC patients formed the retrospective cohort, and preoperative fine-needle aspiration (FNA) specimens from 167 PTC patients formed the prospective cohort. Furthermore, 74 FNA specimens were collected from two additional hospitals to form the external cohort. Droplet digital polymerase chain reaction (ddPCR) was used to detect BRAF V600E mutation status and abundance in the two types of specimens. The relationship between BRAF V600E mutation status and abundance and PTC biological behavior was analyzed in the cohorts. To predict BRAF V600E-positive PTC risk stratification, we constructed postoperative clinicopathological models (Model A, retrospective; Model B, prospective), a preoperative clinical model (Model C), and a fusion model combining BRAF V600E mutation abundance and preoperative clinical information (Model D). The area under the curve (AUC) values were used to assess the performance of these models. Results Univariate and multivariate analysis of the retrospective, prospective and external cohorts indicated that BRAF V600E mutation abundance, not status, was significantly associated with PTC biological behavior. An increase in BRAF V600E mutation abundance was significantly associated with an increased risk of BRAF V600E-positive PTC. The AUCs of model A, model B, model C, and model D in the validation sets were 0.89 (95% CI, 0.83–0.94), 0.89 (95% CI, 0.83–0.99), 0.65 (95% CI, 0.48–0.82), and 0.86 (95% CI, 0.75–0.98), respectively. The AUCs of model B, model C, and model D in the external sets were 0.78(95% CI, 0.67–0.88), 0.61(95% CI, 0.48–0.75) and 0.82 (95% CI, 0.71–0.93), respectively. The AUC of model D was higher than that of model C in the external validation set by 21% (P = 0.02). Conclusions BRAF V600E mutation abundance, not status, reflects PTC biological behavior. Integrating BRAF V600E mutation abundance and preoperative clinical information can be used to better preoperatively predict BRAF V600E-positive PTC risk and guide clinical decision making. Trial registration ChiCTR, ChiCTR2300071472. Registered 31 July 2016 - Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=190478 .https://doi.org/10.1186/s12967-025-06493-4Thyroid cancerBRAF V600E mutation abundanceRisk stratificationMachine learningClinical decision |
| spellingShingle | Yeqin Ni Ping Song Xiangfeng Lin Jingjing Shi Qian Shi Yuanhui Li Siyu Zhu Tianhan Zhou Yanping Xun Shirong Zhang Xingchang Ren Kaining Lu Fan Wu Wei Wang Pan Zhao Rongjing Zhou Wenhua Zhang Dandan Li Jiaoping Zhang Chuanghua Chen Linlin Mao Li Zhou Gang Pan You Peng Yunxian Yu Yuying Chen Rong Ni Guhan Luo Yu Zhang Jugao Fang Haitao Zheng Dingcun Luo Can mutation abundance assess the biological behavior of BRAF V600E-positive papillary thyroid carcinoma? Journal of Translational Medicine Thyroid cancer BRAF V600E mutation abundance Risk stratification Machine learning Clinical decision |
| title | Can mutation abundance assess the biological behavior of BRAF V600E-positive papillary thyroid carcinoma? |
| title_full | Can mutation abundance assess the biological behavior of BRAF V600E-positive papillary thyroid carcinoma? |
| title_fullStr | Can mutation abundance assess the biological behavior of BRAF V600E-positive papillary thyroid carcinoma? |
| title_full_unstemmed | Can mutation abundance assess the biological behavior of BRAF V600E-positive papillary thyroid carcinoma? |
| title_short | Can mutation abundance assess the biological behavior of BRAF V600E-positive papillary thyroid carcinoma? |
| title_sort | can mutation abundance assess the biological behavior of braf v600e positive papillary thyroid carcinoma |
| topic | Thyroid cancer BRAF V600E mutation abundance Risk stratification Machine learning Clinical decision |
| url | https://doi.org/10.1186/s12967-025-06493-4 |
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