背景:甲状腺分化评分(TDS),根据控制甲状腺代谢和功能的16个基因的mRNA表达水平计算,已被提出作为量化PTC差异的一种措施。这项研究的目的是确定TDS是否与患者队列的生存结果相关。
方法:使用两个独立的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果是无进展间隔(PFI)。还探讨了与总生存期(OS)的关联。使用Kaplan-Meier方法和Cox比例风险模型进行生存分析。
结果:在这两个队列中,TDS与诊断时的肿瘤和淋巴结分期以及肿瘤驱动突变状态相关。在队列的单变量分析中,高TDS与更长的PFI相关。在针对整个阶段进行调整后,仅在MDACC队列中,TDS仍与PFI显着相关(aHR0.67,95CI0.52-0.85)。在按肿瘤驱动突变状态分层的亚组分析中,在校正总体分期后,在BRAFV600E突变的肿瘤中,更高的TDS与更长的PFI最为一致(TCGA:aHR0.60,95%CI:0.33-1.07;MDACC:aHR0.59,95%CI:0.42-0.82).对于操作系统,在整个MDACC队列中,增加的TDS与更长的OS相关(aHR=0.78,95%CI:0.63-0.96),其中中位随访时间为12.9年.
结论:TDS可量化PTC的分化状态谱,可作为PTC的潜在预后生物标志物,主要是在BRAFV600E突变的肿瘤中。
BACKGROUND: 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 PTC. The objective of this study is to determine whether TDS is associated with survival outcomes across patient cohorts.
METHODS: Two independent cohorts of PTC patients 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.
RESULTS: 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 (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 across cohorts 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.
CONCLUSIONS: 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.