Background: Radioactive iodine (RAI) therapy is a core part of differentiated thyroid cancer (DTC) treatment. To predict patients' response to RAI is a contributing factor in improving their prognosis and extending their survival. We aimed to investigate the clinical significance of EGFR exon 20, BRAF V600e, and KRAS G13V variants in DTC patients and their predictive role in patients' responses to RAI.

Methods: 117 DTC patients receiving radioactive iodine (I-131) therapy were included; from each, 5 ml of venous blood samples was obtained before RAI treatment, and 3 ml of venous blood samples was obtained after 3 months of treatment. Polymerase chain reaction (PCR) was used to detect the forementioned mutations, and TgAb and TSH were assessed to evaluate DTC patients' response to RAI therapy.

Results: Data showed that EGFR exon 20, BRAF V600e and KRAS G13V mutations were significantly associated with higher TgAbs levels, advanced clinical stage, and positive vascular invasion. EGFR exon 20 and BRAF V600e are associated with larger tumor size. Patients with BRAF V600e and KRAS G13V required higher I-131 doses during RAI and only KRAS was associated with distant metastasis. The co-existence of all three mutations was correlated with higher TgAbs, clinical stage, vascular invasion, larger tumor size, and higher I-131 dose.

Conclusions: EGFR exon 20/BRAF V600e/KRAS G13V mutations are associated with advanced clinical stage and higher radioiodine dose requirements for DTC patients' treatment, indicating a significant role in the disease progression of DTC patients and its impact on predicting their response to RAI therapy.