{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:47:36Z","timestamp":1787503656495,"version":"build-2736575974"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Papillary thyroid carcinoma (PTC) requires improved risk stratification through molecular profiling, yet how mutation interactions shape clinical outcomes remains poorly defined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified three key molecular features: <jats:italic>BRAF<\/jats:italic> mutations (47.2%) predicted recurrence risk (p &amp;lt; 0.001), <jats:italic>TP53<\/jats:italic> mutations (15.3%) were more prevalent in advanced thyroid cancers, and mutual exclusivity between <jats:italic>BRAF<\/jats:italic> and <jats:italic>RET<\/jats:italic>\/<jats:italic>NRAS<\/jats:italic> mutations (p &amp;lt; 0.01), defining distinct oncogenic pathways. Paradoxically, <jats:italic>BRAF<\/jats:italic> 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>By integrating <jats:italic>BRAF<\/jats:italic>\/<jats:italic>TP53<\/jats:italic> 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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1584618","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T04:12:33Z","timestamp":1759119153000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Mutation interactions of BRAF and TP53 define novel prognostic stratification and therapeutic implications in papillary thyroid carcinoma"],"prefix":"10.3389","volume":"16","author":[{"given":"Li","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.7189\/jogh.14.04090","article-title":"Assessing and projecting the 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