Prognostic Significance of Key Molecular Markers in Thyroid Cancer: A Systematic Literature Review and Meta-Analysis.

Thyroid cancer (TC) involves diverse genetic alterations, with their prognostic significance often debated. This study evaluates the impact of , promoter, , and PI3K pathway mutations detected via Next-Generation Sequencing (NGS) on overall survival (OS) and disease-free survival (DFS) in follicular-derived TC patients. A comprehensive search was conducted in MEDLINE, Scopus, and EMBASE databases from 2013 to 2023 for studies using NGS on TC patients. Hazard ratios (HR) and 95% confidence intervals (CI) for OS and DFS were extracted from original studies or estimated from Kaplan-Meier curves (KMC). A random-effects model, weighted by inverse variance, was used to calculate pooled HRs. Publication bias was assessed using Egger's regression test and visual funnel plot analysis. Of the 3921 initial studies, nine studies involving 1075 patients were included in the meta-analysis. mutations showed no significant effect on OS (HR = 1.11, 95% CI: 0.66-1.88) or DFS (HR = 1.23, 95% CI: 0.66-2.29). In contrast, promoter mutations were strongly associated with worse OS (HR = 1.90, 95% CI: 1.17-3.09) and DFS (HR = 2.76, 95% CI: 1.86-4.10). and PI3K pathway mutations were linked to shorter OS (HR = 2.87, 95% CI: 1.44-5.86 and HR = 2.17, 95% CI: 1.05-4.15, respectively), though their impact on DFS remains unclear due to limited data. These findings highlight promoter mutations as strong prognostic markers for both OS and DFS, while and PI3K mutations indicate higher mortality risk.