Correlation analysis between BRAF^V600E mutation and invasiveness of papillary thyroid carcinoma with efficacy of ¹³¹I therapy

Objective To investigate the correlation between the B-Raf proto-oncogene, serine/threonine protein kinase (BRAF)^V600E gene mutation and the clinical characteristics of papillary thyroid carcinoma (PTC) and evaluate its prognostic value in predicting the efficacy of ¹³¹I therapy.

Methods A retrospective analysis was conducted on the clinical data of 291 patients with PTC who underwent ¹³¹I therapy at Tianjin Medical University General Hospital between April 2018 and April 2023. The patients included 100 males and 191 females, with an age of (43.4±12.8) years, ranging from 18 to 74 years. Patients were divided into mutation and wild-type groups on the basis of BRAF^V600E gene test results. Pathological staging and age grouping were performed in accordance with the eighth edition of the tumor, node, metastasis staging system of the American Joint Committee on Cancer. According to the Guidelines for ¹³¹I Therapy of Differentiated Thyroid Cancer (2021 Edition), treatment response was categorized as excellent response (ER), indeterminate response (IDR), biochemical incomplete response (BIR), structural incomplete response (SIR), and assessed at three time points: half a year to one year (short term), three years (midterm), and five years (long term). Comparisons of measurement data between groups were performed by using the independent samples t-test or Mann-Whitney U test, whereas comparisons among multiple groups were conducted by utilizing one-way ANOVA or the Kruskal-Wallis H test. Count data were compared by applying the chi-squared test. A multivariate Logistic regression model was employed to analyze the influence of the BRAF^V600E mutation and other factors on the efficacy of ¹³¹I therapy in patients with PTC.

Results The mutation group comprised 225 patients (77.3%, 225/291), and the wild-type group comprised 66 patients (22.7%, 66/291). Compared with the wild-type group, the mutation group had a significantly higher proportion of males (38.2% vs. 21.2%, χ²=6.55, P=0.007) and a lower incidence of vascular tumor thrombus (1.8% vs. 10.6%, χ²=10.94, P=0.001). The wild-type group was associated with a higher N stage (68.2% vs. 43.1%, χ²=15.41, P<0.001) and a higher distant metastasis rate (9.1% vs. 0.4%, χ²=16.25, P=0.001) than the mutation group. In the one-year response assessment after ¹³¹I therapy, a comparison between the mutation and wild-type groups showed a statistically significant difference in ER, BIR, SIR, and IDR rates (71.1% vs. 62.1%, 8.9% vs. 7.6%, 3.1% vs. 12.1%, 16.9% vs. 18.2%; χ²=8.79, P=0.032). Multivariate Logistic regression model analysis revealed that gender is an independent influencing factor for the BRAF^V600E gene mutation, the probability of harboring a BRAF^V600E mutation was 2.298 times higher in males than in females (OR=2.298, 95%CI: 1.201–4.395, P=0.012). Half-year treatment response assessment: for each one-month increase in the time interval between surgery and ¹³¹I therapy, the risk of achieving SIR (compared with ER) increased by 8.1% (OR=1.081, 95%CI: 1.014–1.153; P=0.017). Three-year trestment response assessmengt: for each one-year increase in age, the risk of achieving BIR (compared with ER) increased by 16.2% (OR=1.162, 95%CI: 1.001–1.349; P=0.048).

Conclusions The BRAF^V600E gene mutation was correlated only with gender (higher risk in males) and was an independent risk factor for PTC. It lacked a significant correlation with enhanced PTC invasiveness or reduced ¹³¹I therapy efficacy. Age was a key determinant of midterm (three years) treatment response. The interval between surgery and ¹³¹I therapy should be shortened, provided that the surgical wound has healed adequately, to optimize short term (half a year) efficacy.