Prognostic impact of RAS mutation on papillary thyroid carcinoma: a systematic review and meta-analysis

Papillary thyroid carcinoma (PTC) is the most common form of thyroid malignancy, and activating mutations in the RAS gene family have been implicated in its pathogenesis and clinical behavior. This study aimed to evaluate the role of RAS mutations in clinical outcomes of patients with PTC.

We conducted a comprehensive literature search of PubMed, Scopus, and WOS. Eligible studies included data on RAS mutation prevalence and at least one of the predefined endpoints. Hazard ratios (HR) for recurrence-free survival (RFS), odds ratios (OR) for mortality, distant metastasis, and tumor recurrence, and mean differences (MD) for tumor size were used as effect sizes.

A total of 22 studies, involving 4727 patients, were included in this analysis. The pooled prevalence of RAS mutations was 20% (95% CI: 14%-28%). Presence of RAS mutation was associated with significantly higher odds of distant metastasis (OR = 3.12, 95% CI: 1.48-6.59, p < 0.01), while no significant associations were found with RFS (HR = 1.05, 95% CI: 0.52-2.13, p = 0.88), overall mortality (OR = 2.01, 95% CI: 0.60-6.70, p = 0.21), tumor recurrence (OR = 0.35; 95% CI: 0.08-1.61, p = 0.13). Moreover, our findings revealed no significant differences in tumor size between RAS-positive and RAS-negative cases (MD = 0.01, 95% CI: -0.73-0.72, p = 0.96).

RAS mutations are present in 20% of PTC cases and are associated with increased risk of distant metastasis. However, these mutations were not significantly associated with other clinical outcomes. These findings support the integration of RAS mutation testing into postoperative risk stratification to identify patients who may benefit from more intensive surveillance and personalized therapeutic strategies.