Decoding RAS mutations in thyroid cancer: A meta-analysis unveils specific links to distant metastasis and increased mortality

BACKGROUND/OBJECTIVES: RAS mutations are common in thyroid cancer, but their impact on clinical outcomes remains controversial. This study aimed to evaluate the prevalence of RAS mutations in thyroid cancer and their association with various clinical and pathological features. METHODS: We conducted a systematic review and meta-analysis of studies reporting on RAS mutations in thyroid cancer. Both one-arm and pairwise meta-analyses were performed to compare outcomes between RAS-mutated (RAS+) and wild-type (RAS-) thyroid cancers. RESULTS: Our analysis included 2552 thyroid cancer patients from 17 studies. The overall prevalence of RAS mutations was 35.4 % (95 % CI: 22.7 %-50.7 %). NRAS mutations were most common (69.47 %, 95 % CI: 66.15 %-72.66 %), followed by HRAS (25.83 %, 95 % CI: 22.77 %-29.14 %) and KRAS (6.92 %, 95 % CI: 5.27 %-9.04 %). No statistically significant differences were found between RAS+ and RAS- cases in rates of T1/2 tumors, lymph node metastasis, extrathyroidal extension, or recurrence. The risk of distant metastasis was significantly higher in RAS+ cases (15 %, 95 % CI: 6 %-34 %) compared to RAS- cases (4 %, 95 % CI: 1 %-12 %), with a relative risk of 3.23 (95 % CI: 1.49-7.02). Notably, RAS+ cases showed a significantly higher mortality rate (8 %, 95 % CI: 3 %-18 %) compared to RAS- cases (2 %, 95 % CI: 1 %-5 %), with a relative risk of 4.36 (95 % CI: 1.23-15.50, p = 0.03). CONCLUSION: While RAS mutations are prevalent in thyroid cancer, they do not significantly impact most clinical and pathological features. However, the presence of RAS mutations is associated with a significantly higher risk of distant metastasis and mortality, suggesting their potential role as a prognostic marker in thyroid cancer. These findings underscore the importance of RAS mutation testing in risk stratification and treatment planning for thyroid cancer patients.