TCR-Seq Identifies Distinct Repertoires of Distant-Metastatic and Nondistant-Metastatic Thyroid Tumors

J Clin Endocrinol Metab. 2020 Sep 1;105(9):dgaa452. doi: 10.1210/clinem/dgaa452.

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.

Keywords: ROC curve; TCR-seq; distant-metastatic PTC classifier; thyroid cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, T-Cell Receptor beta*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Retrospective Studies
  • Thyroid Cancer, Papillary / genetics*
  • Thyroid Cancer, Papillary / pathology*
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology*
  • Thyroid Nodule / genetics
  • Thyroid Nodule / pathology

Substances

  • Receptors, Antigen, T-Cell