Department of Head and Neck Surgery, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China.
Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Institute of Cancer and Basic Medicine, Chinese Academy of Sciences Hangzhou, China.
J Clin Endocrinol Metab. 2020 Sep 1;105(9). doi: 10.1210/clinem/dgaa452.
Malignant thyroid tumor with distant metastasis is associated with poor outcome. Early detection of distant metastasis is of great clinical importance.
Thyroid tumor infiltrated with T cells can serve as a biomarker for monitoring metastasis.
A retrospective analysis was performed of patient clinical samples collected between 2012 to 2018, using T-cell receptor sequencing (TCR-seq) for clinical exploration.
This study took place at Zhejiang Cancer Hospital.
Sixty-eight patients with papillary thyroid cancer (PTC) (distinct metastatic status) and 21 patients with benign nodules were enrolled. All patients had not received any treatment before surgery.
The characteristics of TCRβ complementary-determining region 3 (CDR3) for each patient were determined by high-throughput sequencing.
The TCRβ diversity of malignant tumors is significantly higher than benign nodules both in blood and tumor samples (Shannon index, blood, P < .01; tumor, P < .001). The malignant tumors with distant metastasis or invasiveness showed lower TCRβ diversity than nonmetastasis (Shannon index, P < .01) or noninvasive (Shannon index, P < .01) malignant tumors. Analysis of the Morisita-Horn similarity index indicated significant TCRβ repertoire similarity between tumor and blood in distant-metastatic patients (comparison with nonmetastasis, P < .05). According to the discrepancy of the CDR3 among patients with different clinicopathological status, the classifier was constructed to discriminate distant-metastatic individuals. A promising area under the curve value of 83.8% was obtained with the number of overlapping CDR3 clonotypes.
The availability and reliability of TCR-seq render it prospective to translate these intrinsic attributes into clinical practice for monitoring distant metastasis in PTC patients.
甲状腺恶性肿瘤伴远处转移与不良预后相关。早期发现远处转移具有重要的临床意义。
甲状腺浸润 T 细胞的肿瘤可作为监测转移的生物标志物。
回顾性分析了 2012 年至 2018 年间收集的患者临床样本，采用 T 细胞受体测序（TCR-seq）进行临床探索。
浙江省肿瘤医院。
纳入 68 例甲状腺乳头状癌（PTC）（转移状态不同）患者和 21 例良性结节患者。所有患者在手术前均未接受任何治疗。
通过高通量测序确定每位患者 TCRβ互补决定区 3（CDR3）的特征。
恶性肿瘤的 TCRβ多样性在血液和肿瘤样本中均明显高于良性结节（Shannon 指数，血液，P<.01；肿瘤，P<.001）。远处转移或侵袭性的恶性肿瘤的 TCRβ多样性低于非转移（Shannon 指数，P<.01）或非侵袭性（Shannon 指数，P<.01）恶性肿瘤。Morisita-Horn 相似性指数分析表明，远处转移患者肿瘤与血液之间的 TCRβ库具有显著的相似性（与非转移患者比较，P<.05）。根据不同临床病理状态患者间 CDR3 的差异，构建了分类器以区分远处转移个体。重叠 CDR3 克隆型数量的曲线下面积为 83.8%，具有较好的预测价值。
TCR-seq 的可用性和可靠性使其有望将这些内在特征转化为 PTC 患者监测远处转移的临床实践。
