RAI therapy is only effective if the tumor cells can absorb iodine. However, up to 15% of patients with PTC – and about 50% of those with metastatic disease – show low or no iodine uptake, making the treatment ineffective and delaying other potentially better options.

In this study, researchers analyzed gene expression in 36 tumor samples where iodine uptake was measured directly in the tissue after surgery. Using RNA sequencing, they identified 63 genes that were differently expressed between tumors with high and low iodine avidity. One gene, ANO1, stood out as a strong candidate biomarker. ANO1 is a known iodine transporter located in the membrane of thyroid cells, and its expression correlated significantly with iodine uptake.

Other deregulated genes pointed to biological processes involved in thyroid hormone production and key signaling pathways like PI3K-AKT and MAPK – both known to influence cancer behavior and treatment response.

The team also developed a predictive model combining ANO1 expression, tumor subtype, and tissue type. The model performed well, suggesting that gene profiling could help identify patients unlikely to benefit from RAI therapy early on – potentially guiding them toward alternative treatments sooner.

This study represents a step toward more personalized care in thyroid cancer, where molecular profiling could help avoid ineffective therapies and improve outcomes for patients with challenging tumors.

Source – Karolinska Institutet