Potential of the   FOX gene family and LncRNAs as biomarkers in differentiated thyroid cancer treated with I-131

Objectives Forkhead box (FOX) transcription factors and long non-coding RNAs (lncRNAs) localize within tumor cell nuclei in various cancers, suggesting their involvement in transcriptional regulation. This study aimed to investigate expression changes of FOX family members and selected lncRNAs to explore their potential regulatory roles in differentiated thyroid cancer (DTC). Methods Expression levels of FOX genes and lncRNAs were analyzed using RT-PCR, and protein levels were measured via ELISA in patients diagnosed with DTC who received radioactive iodine (RAI) therapy. Results RT-PCR analysis revealed significant differences in FOXO1 and HOXA11-AS expression before and after RAI therapy (p<0.05). FOXO3 , FOXP1 , FOXP2 , and CASC21 showed significant expression differences in pre-RAI samples, while MEG3 and KCNQ1OT1 differed significantly post-RAI (p<0.05). Moreover, strong correlations were identified between FOXO3 , FOXP2 , and key lncRNAs including MEG3 , KCNQ1OT1 , CASC21 , and HOXA11-AS (p<0.05). ELISA results showed a significant change in FOXP1 protein levels, and TSH and Tg levels differed significantly across treatment stages (p<0.05). CASC21 exhibited the highest AUC in ROC analysis. Conclusions Despite the limited sample size, the findings suggest the potential of these genes, particularly CASC21, as biomarkers in DTC. These results may contribute to enhancing RAI therapy efficacy and advancing personalized treatment approaches.