Recurrence of papillary thyroid cancer: a systematic appraisal of risk factors

Hannah Nieto, Caitlin Thornton, Katie Brookes, Albert Nobre De Menezes, Alice Fletcher, Mohammed Alshahrani, Merve Kocbiyik, Neil Sharma, Kristien Boelaert, Jean-Baptiste Cazier, Hisham Mehanna, Vicki Smith, Martin Read, Christopher McCabe

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Abstract Context Thyroid cancer recurrence is associated with increased mortality and adverse outcomes. Recurrence risk is currently predicted using clinical tools, often restaging patients after treatment. Detailed understanding of recurrence risk at disease onset could lead to personalized and improved patient care. Objective We aimed to perform a comprehensive bioinformatic and experimental analysis of 3 levels of genetic change (mRNA, microRNA, and somatic mutation) apparent in recurrent tumors and construct a new combinatorial prognostic risk model. Methods We analyzed The Cancer Genome Atlas data (TCGA) to identify differentially expressed genes (mRNA/microRNA) in 46 recurrent vs 455 nonrecurrent thyroid tumors. Two exonic mutational pipelines were used to identify somatic mutations. Functional gene analysis was performed in cell-based assays in multiple thyroid cell lines. The prognostic value of genes was evaluated with TCGA datasets. Results We identified 128 new potential biomarkers associated with recurrence, including 40 mRNAs, 39 miRNAs, and 59 genetic variants. Among differentially expressed genes, modulation of FN1, ITGα3, and MET had a significant impact on thyroid cancer cell migration. Similarly, ablation of miR-486 and miR-1179 significantly increased migration of TPC-1 and SW1736 cells. We further utilized genes with a validated functional role and identified a 5-gene risk score classifier as an independent predictor of thyroid cancer recurrence. Conclusion Our newly proposed risk model based on combinatorial mRNA and microRNA expression has potential clinical utility as a prognostic indicator of recurrence. These findings should facilitate earlier prediction of recurrence with implications for improving patient outcome by tailoring treatment to disease risk and increasing posttreatment surveillance.
Original languageEnglish
Pages (from-to)1392–1406
Number of pages15
JournalJournal of Clinical Endocrinology and Metabolism
Issue number5
Early online date16 Nov 2021
Publication statusE-pub ahead of print - 16 Nov 2021

Bibliographical note

© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.


  • miRNA
  • TCGA
  • recurrence
  • thyroid
  • Papillary
  • Biochemistry, medical
  • Clinical Biochemistry
  • Biochemistry
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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