Mutation interactions of BRAF and TP53 define novel prognostic stratification and therapeutic implications in papillary thyroid carcinoma

Background Papillary thyroid carcinoma (PTC) requires improved risk stratification through molecular profiling, yet how mutation interactions shape clinical outcomes remains poorly defined. Methods This single-center retrospective study analyzed 72 PTC cases using next-generation sequencing to characterize mutation patterns and pathway evolution, with validation against The Cancer Genome Atlas datasets. Results We identified three key molecular features: BRAF mutations (47.2%) predicted recurrence risk (p < 0.001), TP53 mutations (15.3%) were more prevalent in advanced thyroid cancers, and mutual exclusivity between BRAF and RET / NRAS mutations (p < 0.01), defining distinct oncogenic pathways. Paradoxically, BRAF mutations correlated with survival improvement (hazard ratio = 0.397), challenging conventional prognostic models. Pathway analysis revealed a potential shift from MAPK dominance in PTC to PI3K/NOTCH activation in advanced thyroid cancers, suggesting targetable vulnerabilities for mTOR inhibitors. Conclusion By integrating BRAF / TP53 status with conventional staging, we establish a mutation-guided framework that may refine risk prediction and inform treatment strategies, bridging molecular heterogeneity with clinical decision-making. This work provides insights for personalizing thyroid cancer management.