Department of Endocrinology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province, China.
Department of Translational Medicine, Genetron Health (Beijing) Technology, Co. Ltd., Beijing, China.
Endocrine. 2022 Nov;78(2):296-305. doi: 10.1007/s12020-022-03154-0. Epub 2022 Aug 12.
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.
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.
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.
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.
尽管甲状腺乳头状癌（PTC）的死亡率较低，但复发率仍相对较高。本研究旨在开发一种分子特征来预测 PTC 的复发。
共纳入 333 例来自癌症基因组图谱（TCGA）的 PTC 患者数据。我们计算了肿瘤突变负担（TMB）并分析了 BRAF 和 TERT 启动子的突变状态。
在 TMB-L 患者中，17 例发生肿瘤复发，而在 TMB-H 患者中，70 例发生肿瘤复发（风险比 [HR]，3.55；95%置信区间 [CI]，1.75-7.21；P < 0.001）。在调整经典临床病理因素（患者年龄、性别、甲状腺外侵犯和淋巴结转移）后，TMB-H 患者的复发 HR 仍然显著。这些临床因素对 TMB-L 患者的复发率没有影响，但对 TMB-H 患者的预后有很强的不利影响。与缺乏突变的 TMB-L 患者相比，同时存在 BRAF V600E 和/或 TERT C228/250T 突变的 TMB-H 患者的复发 HR（95%CI）为 6.68（2.41-18.57），在调整临床病理因素后仍有统计学意义。BRAF V600E 和 TERT C228/250T 的突变状态对 TMB-L 患者的 PTC 复发影响不大。在 TMB-H 患者中，任一突变均与高复发率相关。
BRAF V600E 和/或 TERT 启动子突变的存在表明 TMB-H 患者复发风险高。这代表了一种强大的分子预后基因型，可以帮助预测复发风险最高的患者。
