Mu Zhuanzhuan, Zhang Xin, Liang Dongquan, Fang Jugao, Chen Ge, Guo Wenting, Sun Di, Sun Yuqing, Kai Zhentian, Huang Lisha, Liang Jun, Lin Yansong
Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences & PUMC, Beijing 100730, China.
Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing 100730, China.
Chin J Cancer Res. 2024 Feb 29;36(1):25-35. doi: 10.21147/j.issn.1000-9604.2024.01.03.
Patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.
Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel (ThyroLead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification (MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.
A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIR-DTC. Genetic alterations were identified in 90% of all the patients, with (59.7% . 17.3%), promoter (43.9% 7.4%), and mutations (11.5% 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for fusions (15.8% 39.5%), which had the opposite pattern. and promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness (P<0.001), with an odds ratio (OR) of high to low MRS of 7.52 [95% confidence interval (95% CI), 3.96-14.28; P<0.001] and an OR of intermediate to low MRS of 3.20 (95% CI, 1.01-10.14; P=0.041).
Molecular alterations were associated with RAI refractoriness, with and promoter mutations being the predominant contributors, followed by and mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.
放射性碘难治性分化型甲状腺癌（RAIR-DTC）患者常被延迟诊断，且治疗选择有限。RAI难治性与潜在基因特征之间的相关性尚未得到广泛研究。
纳入成年远处转移性DTC患者，安排其接受定制的26基因panel（ThyroLead）的二代测序。将患者分为RAIR-DTC组或非RAIR组，以确定临床病理和分子特征的差异。基于所识别的分子改变与RAI难治性之间的关联构建分子风险分层（MRS），结果分为高、中或低MRS。
共纳入220例远处转移患者，其中63.2%被确定为RAIR-DTC。所有患者中有90%发现基因改变，其中，（59.7% 对17.3%）、启动子（43.9% 对7.4%）和突变（11.5% 对3.7%）在RAIR-DTC组比非RAIR组更常见，除了融合（15.8% 对39.5%）呈现相反模式。和启动子是RAIR-DTC的独立预测因素，占RAIR-DTC患者的67.6%。MRS与RAI难治性密切相关（P<0.001），高MRS与低MRS的比值比（OR）为7.52 [95%置信区间（95%CI），3.96 - 14.28；P<0.001]，中MRS与低MRS的OR为3.20（95%CI，1.01 - 10.14；P = 0.041）。
分子改变与RAI难治性相关，和启动子突变是主要因素，其次是和突变。MRS可能是预测临床结局和指导精准治疗干预的有价值工具。
