Tumor mutation burden-assisted risk stratification for papillary thyroid cancer

Abstract

Purpose: Although papillary thyroid cancer (PTC) has a low mortality rate, the rate of recurrence remains relatively high. This study aims to develop a molecular signature to predict the recurrence of PTC.

Methods: A total of 333 PTC patients' data from The Cancer Genome Atlas (TCGA) were included. We calculated tumor mutation burden (TMB) and analyzed the mutation status of BRAF and TERT promoter.

Results: Tumor recurrence occurred in 17 of 263 cases in TMB-L patients versus 14 of 70 cases in TMB-H patients (hazard ratio [HR], 3.55; 95% confidence interval [CI], 1.75-7.21; P < 0.001). The HR for recurrence in TMB-H patients remained significant after adjustment for classical clinicopathologic factors (patient age, gender, extrathyroidal extension and lymph node metastasis). These clinical factors had no effect on recurrence rate in TMB-L patients, but had a strong adverse effect on the prognosis of TMB-H patients. Compared with TMB-L patients lacking mutation, the HR (95% CI) of recurrence for TMB-H patients with coexisting BRAF V600E and/or TERT C228/250 T mutations was 6.68 (2.41-18.57), which remained significant after adjustment for clinicopathological factors. The mutation status of BRAF V600E and TERT C228/250 T had little effect on PTC recurrence in TMB-L patients. Either of the mutation was associated with high recurrence rate in TMB-H patients.

Conclusions: The presence of BRAF V600E and/or TERT promoter mutations denotes a high risk of recurrence in TMB-H patients. This represents a powerful molecular prognostic genotype that can help predict patients with the highest risk of recurrence.

Keywords: Molecular analysis; Thyroid cancer; Tumor mutation burden; Tumor recurrence.