Xiabin Lan 1,2 , Jun Cao 2 , Ke Ye 2,3 , Chao Zhang 4 , Qihong Zhang 5 , Xinyang Ge 2,6 , Changxi Wang 4,7 , Chunliu Zhang 8 , Zaixian Tai 4 , Wei Wei 4 , Yi Huang 4 , Xin Yi 4 , Zhuo Tan 1 , Chuanming Zheng 9 , Chao Chen 1 , Xin Zhu 2 , Jiafeng Wang 1 , Jiajie Xu 9 , Xuhang Zhu 1 , Minghua Ge 9 Show Affiliations »
Abstract
CONTEXT: Malignant thyroid tumor with distant metastasis is associated with poor outcome. Early detection of distant metastasis is of great clinical importance. OBJECTIVE: Thyroid tumor infiltrated with T cells can serve as a biomarker for monitoring metastasis. DESIGN: A retrospective analysis was performed of patient clinical samples collected between 2012 to 2018, using T-cell receptor sequencing (TCR-seq) for clinical exploration. SETTING: This study took place at Zhejiang Cancer Hospital. PATIENTS: 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. MAIN OUTCOME MEASURE: The characteristics of TCRβ complementary-determining region 3 (CDR3) for each patient were determined by high-throughput sequencing. RESULTS: 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. CONCLUSION: 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. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
CONTEXT: Malignant thyroid tumor with distant metastasis is associated with poor outcome. Early detection of distant metastasis is of great clinical importance. OBJECTIVE: Thyroid tumor infiltrated with T cells can serve as a biomarker for monitoring metastasis. DESIGN: A retrospective analysis was performed of patient clinical samples collected between 2012 to 2018, using T-cell receptor sequencing (TCR-seq ) for clinical exploration. SETTING: This study took place at Zhejiang Cancer Hospital. PATIENTS : 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. MAIN OUTCOME MEASURE: The characteristics of TCRβ complementary-determining region 3 (CDR3 ) for each patient were determined by high-throughput sequencing. RESULTS: 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. CONCLUSION: 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 . © Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Entities: Chemical
Disease
Gene
Species
Keywords:
ROC curve; TCR-seq; distant-metastatic PTC classifier; thyroid cancer
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Year: 2020
PMID： 32674137 DOI： 10.1210/clinem/dgaa452
Source DB: PubMed Journal: J Clin Endocrinol Metab ISSN： 0021-972X Impact factor: 5.958