# The ability of anexelekto (AXL) expression and TERT promoter mutation to predict radioiodine-refractory differentiated thyroid carcinoma

## TL;DR

This study identifies AXL expression and TERT promoter mutations as potential predictors of radioiodine-refractory thyroid cancer, which could help guide treatment decisions.

## Contribution

The study introduces AXL expression and TERT promoter mutation as novel independent predictors of RAI-refractory differentiated thyroid carcinoma.

## Key findings

- AXL expression was significantly higher in RAI-refractory DTC patients compared to non-refractory cases.
- TERT promoter mutations were more common in RAI-refractory DTC patients.
- Aggressive tumor subtype, AXL expression, and TERT mutation independently correlate with RAI refractoriness.

## Abstract

Differentiated thyroid carcinoma (DTC) generally has a favourable prognosis with standard treatments; however, the risks of local recurrence and distant metastases remain a concern, affecting a substantial proportion of patients. Radioactive iodine (RAI) refractoriness further complicates DTC management, leading to substantially reduced survival rates. In this study, we aimed to identify anexelekto (AXL) expression and TERT promoter mutation as potential predictors of RAI-refractory DTC.

We conducted a retrospective analysis of 81 DTC patients who underwent thyroidectomy and received at least two courses of RAI therapy. After a median follow-up period of 30 months (range: 6–60 months), therapy response was categorized as nonrefractory or refractory. AXL expression and TERT promoter mutation were evaluated in all patients to discern any associations with the development of RAI refractoriness.

The overall prevalence of refractory RAI in DTC patients was 44.4% (36/81). AXL expression was high in 30/36 patients (83.3%) with RAI-refractory DTC and negative/low in 24/45 patients (53.3%) with non-RAI-refractory DTC (OR adjusted: 44.98, CI 95%: 1.41-1439.03, p = 0.031). TERT promoter mutation occurred in 21/36 (58.3%) RAI-refractory DTCs and in 2/45 (4.4%) non-RAI-refractory DTCs (OR adjusted: 10.95, CI 95%: 1.06-112.92, p = 0.044). Despite similar age, sex, and histological type distributions between the RAI-refractory and non-RAI-refractory groups, significant differences in clinicopathological characteristics emerged. Multivariate analysis confirmed that aggressive subtype, elevated AXL expression, and TERT promoter mutation independently correlated with RAI-refractory status.

Our predictive model highlights the association of elevated AXL expression, TERT promoter mutation, and an aggressive tumour subtype with the risk of RAI refractoriness. This information has the potential to aid in making informed treatment decisions. Furthermore, AXL is a potential therapeutic target for RAI-refractory disease.