Wijewardene Ayanthi, Clifton-Bligh Roderick J, Wang Bin, Luxford Catherine, Robinson Bruce G, Bullock Martyn, Gild Matti
Endocr Relat Cancer. 2025 Jan 4;32(2). doi: 10.1530/ERC-24-0227. Print 2025 Feb 1.
Liquid biopsies are a minimally invasive approach to obtain biomarkers including cell-free DNA (cfDNA) from peripheral blood. To date, there are limited and conflicting studies evaluating their role in thyroid cancer. Our study evaluated the utility of cfDNA in advanced thyroid cancers. Patients aged >18 years with metastatic medullary thyroid cancer (MTC), poorly differentiated thyroid cancer (PDTC) or anaplastic thyroid cancer (ATC) were enrolled in this prospective study between 2020 and 2024. As part of standard care, sequencing of germline and tumoral DNA was conducted, and patients with germline mutations were excluded from the study. Whole blood samples were collected in Streck cell-free DNA BCT tubes, and cfDNA was extracted from plasma using an EZ1&2 ccfDNA kit and EZ2 Connect. The extracted cfDNA was then sequenced across 50 key cancer-related genes using an Oncomine Precision Assay panel on an Ion Torrent Genexus integrated sequencer. Forty patients were included: 27 MTC, 2 ATC and 11 PDTC. Tumoral mutations were detected in 36 of the included patients (90%): cfDNA detected mutations in 18/36 patients (13 MTC, 1 ATC and 4 PDTC (50%)). The sensitivity of cfDNA was 86% (6/7) pre-tyrosine kinase inhibitor therapy and reduced to 54% on therapy (13/24), suggestive of the lack of tumor-derived DNA shedding with a strong on-target treatment efficacy. The median cfDNA concentration was higher in samples with a detected mutation (n = 43) than those without (n = 26), 11.91 ng/mL vs 5.81 ng/mL, respectively, while an increasing cfDNA was associated with worse progression-free survival (P < 0.01). cfDNA is a novel biomarker with potential to monitor disease progression in patients with advanced thyroid cancers.
液体活检是一种微创方法，用于从外周血中获取包括游离DNA（cfDNA）在内的生物标志物。迄今为止，评估其在甲状腺癌中作用的研究有限且相互矛盾。我们的研究评估了cfDNA在晚期甲状腺癌中的效用。2020年至2024年期间，年龄大于18岁的转移性甲状腺髓样癌（MTC）、低分化甲状腺癌（PDTC）或未分化甲状腺癌（ATC）患者被纳入这项前瞻性研究。作为标准治疗的一部分，进行了种系和肿瘤DNA测序，种系突变患者被排除在研究之外。全血样本收集于Streck游离DNA BCT管中，使用EZ1&2 ccfDNA试剂盒和EZ2 Connect从血浆中提取cfDNA。然后，使用Ion Torrent Genexus集成测序仪上的Oncomine Precision Assay panel对提取的cfDNA进行50个关键癌症相关基因的测序。纳入40例患者：27例MTC、2例ATC和11例PDTC。在所纳入的患者中，36例（90%）检测到肿瘤突变：cfDNA在18/36例患者中检测到突变（13例MTC、1例ATC和4例PDTC（50%））。cfDNA在酪氨酸激酶抑制剂治疗前的敏感性为86%（6/7），治疗时降至54%（13/24），提示缺乏肿瘤衍生DNA脱落且靶向治疗疗效显著。检测到突变的样本（n = 43）中cfDNA的中位浓度高于未检测到突变的样本（n = 26），分别为11.91 ng/mL和5.81 ng/mL，而cfDNA升高与无进展生存期较差相关（P < 0.01）。cfDNA是一种新型生物标志物，有可能监测晚期甲状腺癌患者的疾病进展。
