Wang Jennifer R, Zafereo Mark E, Cabanillas Maria E, Wu Chia Chin, Xu Li, Dai Yaoyi, Wang Wenyi, Lai Stephen Y, Henderson Ying, Erasmus Lauren, Williams Michelle D, Joshu Corinne, Ray Debashree
Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
J Clin Endocrinol Metab. 2025 Jan 21;110(2):356-363. doi: 10.1210/clinem/dgae532.
Thyroid differentiation score (TDS), calculated based on mRNA expression levels of 16 genes controlling thyroid metabolism and function, has been proposed as a measure to quantify differentiation in papillary thyroid carcinoma (PTC).
The objective of this study is to determine whether TDS is associated with survival outcomes across patient cohorts.
Two independent cohorts of patients with PTC were used: (1) The Cancer Genome Atlas (TCGA) thyroid cancer study (N = 372), (2) MD Anderson Cancer Center (MDACC) cohort (N = 111). The primary survival outcome of interest was progression-free interval (PFI). Association with overall survival (OS) was also explored. The Kaplan-Meier method and Cox proportional hazards models were used for survival analyses.
In both cohorts, TDS was associated with tumor and nodal stage at diagnosis as well as tumor driver mutation status. High TDS was associated with longer PFI on univariable analyses across cohorts. After adjusting for overall stage, TDS remained significantly associated with PFI in the MDACC cohort only (adjusted hazard ratio [aHR] 0.67, 95% CI 0.52-0.85). In subgroup analyses stratified by tumor driver mutation status, higher TDS was most consistently associated with longer PFI in BRAFV600E-mutated tumors in the MDACC cohort after adjusting for overall stage (TCGA: aHR 0.60, 95% CI 0.33-1.07; MDACC: aHR 0.59, 95% CI 0.42-0.82). For OS, increasing TDS was associated with longer OS in the overall MDACC cohort (aHR = 0.78, 95% CI 0.63-0.96), where the median duration of follow-up was 12.9 years.
TDS quantifies the spectrum of differentiation status in PTC and may serve as a potential prognostic biomarker in PTC, mostly promisingly in BRAFV600E-mutated tumors.
甲状腺分化评分（TDS）是基于16个控制甲状腺代谢和功能的基因的mRNA表达水平计算得出的，已被提议作为量化甲状腺乳头状癌（PTC）分化程度的一种指标。
本研究的目的是确定TDS是否与不同患者队列的生存结果相关。
使用了两个独立的PTC患者队列：（1）癌症基因组图谱（TCGA）甲状腺癌研究（N = 372），（2）MD安德森癌症中心（MDACC）队列（N = 111）。感兴趣的主要生存结局是无进展生存期（PFI）。还探讨了与总生存期（OS）的关联。采用Kaplan-Meier法和Cox比例风险模型进行生存分析。
在两个队列中，TDS均与诊断时的肿瘤和淋巴结分期以及肿瘤驱动基因突变状态相关。在各队列的单变量分析中，高TDS与较长的PFI相关。在调整总体分期后，仅在MDACC队列中TDS仍与PFI显著相关（调整后风险比[aHR] 0.67，95%可信区间0.52 - 0.85）。在按肿瘤驱动基因突变状态分层的亚组分析中，在调整总体分期后，MDACC队列中BRAFV600E突变肿瘤的较高TDS最一致地与较长的PFI相关（TCGA：aHR 0.60，95%可信区间0.33 - 1.07；MDACC：aHR 0.59，95%可信区间0.42 - 0.82）。对于OS，在整个MDACC队列中TDS升高与较长的OS相关（aHR = 0.78，95%可信区间0.63 - 0.96），该队列的中位随访时间为12.9年。
TDS量化了PTC中的分化状态谱，可能作为PTC中一种潜在的预后生物标志物，在BRAFV600E突变肿瘤中最具前景。
