TCR-seq identifies distinct repertoires of distant metastatic and non-distant metastatic thyroid tumors.

Malignant thyroid tumor with distant metastasis is associated with poor outcome. Early detection of the distant metastasis is of great clinical importance.Thyroid tumor infiltrated T cell can be served as a biomarker for monitoring metastasis.Retrospective analysis was performed of clinical samples from patients collected between 2012 to 2018, using TCR-seq for clinical exploration.Zhejiang Cancer Hospital.68 patients with 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 CDR3 for each patient were determined by High-throughput sequencing.The TCRβ diversity of malignant tumors is significantly higher than benign nodules in both blood and tumor samples (Shannon index, blood, P < 0.01; tumor, P < 0.001). The malignant tumors with distant metastasis or invasiveness showed lower TCRβ diversity than non-metastasis (Shannon index, P < 0.01) or non-invasive (Shannon index, P < 0.01) malignant tumors. Analysis of the Morisita-Horn similarity index indicated that the significant TCRβ repertoires similarity between tumor and blood in distant metastatic patients (Comparison with Non-metastasis, P < 0.05). According to the discrepancy of the CDR3 among patients with different clinicopathological status, the classifier was constructed to discriminate distant metastatic individuals. The promising AUC value 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.

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