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Background  To determine the relevance of the single or combination mutations of BRAF V600E, TERT, and NRAS genes and the clinicopathologic relationship in papillary thyroid cancer (PTC).    Methods  Patients with PTC were enrolled into the study between February 2018 and April 2019. Based on the number of mutant genes, we classified the participants into single BRAF V600E mutation group, double mutations group and no mutation group. Single factor and multiple logistic regression analyses were applied to explore the independent factors. Review Manager 5.3 was used for meta-analysis to review the clinical efficacy of gene co-mutations.    Results  Finally, 483 patients were enrolled into the study and 419 (86.7%) of them harbored BRAF V600E mutation. TERT or NRAS mutation was likely to coexist with BRAF V600E mutation in PTC. BRAF V600E and NRAS promoter co-mutations was identified in 6 patients, with a prevalence of 1.2%. Prevalence of BRAF V600E and TERT coexistence in PTC was 2.1%. Significant differences were found among age, pathology, multifocality, bilateral lesions, lymph node metastasis, and 131I radiotherapy,  P  < 0.01. Multiple logistic regression analyses demonstrated that age [odds ratio (OR) = 1.044, 95%  confidence interval (CI)  = 1.013–1.076;  P  = 0.006], lymph node metastasis [OR = 0.094, 95%  CI  = 0.034–0.264;  P  < 0.001], 131I radiotherapy [OR = 7.628, 95%  CI  = 2.721–21.378;  P  < 0.001] were risk factors for BRAF V600E mutation. Besides, age [OR = 1.135, 95%  CI  = 1.069–1.205;  P  < 0.001], multiple leisions [OR = 4.128, 95%  CI  = 1.026–16.614;  P  = 0.046], pathology [OR = 3.954, 95%  CI  = 1.235–12.654;  P  = 0.021] were independent factors for combination mutations. Meta-analysis showed significant association of BRAF V600E+/TERT+ co-mutations with lymph node metastasis, multifocality, distant metastasis, tumor recurrence, extrathyroidal extension, and dead of disease.    Conclusions  Prevalence of BRAF V600E mutation in Northwest China was higher than other areas. Age, multiple lesions, and pathology were independent factors for double mutation of BRAF V600E/TERT or BRAF V600E/NRAS. Coexistence of BRAF V600E and TERT promoter mutations was significantly correlated with poor outcome.

Relevance and clinicopathologic relationship of BRAF V600E, TERT and NRAS mutations for papillary thyroid carcinoma patients in Northwest China