# Predicting the Metastatic Potential of Papillary Thyroid Microcarcinoma Based on the Molecular Profile of Preoperative Cytology Specimens

**Authors:** Sergei A. Lukyanov, Sergei E. Titov, Aria V. Dzodzaeva, Vladimir E. Vanushko, Dmitry G. Beltsevich, Yuliya A. Veryaskina, Semyon V. Kupriyanov, Ekaterina V. Bondarenko, Ekaterina A. Troshina, Liliya S. Urusova, Sergei V. Sergiyko

PMC · DOI: 10.3390/ijms26136418 · International Journal of Molecular Sciences · 2025-07-03

## TL;DR

This study identifies molecular markers in preoperative cytology samples that can predict the metastatic potential of papillary thyroid microcarcinoma.

## Contribution

The study introduces a set of molecular markers for preoperative prediction of metastasis in PTMC patients.

## Key findings

- HMGA2, TIMP1, FN1, and miR-146b are upregulated in metastatic PTMC.
- miR-7 and miR-148b are downregulated in metastatic PTMC.
- DIO1, TFF3, TPO, and SLC26A7 show significant reductions in metastatic tumors.

## Abstract

The strategy of active surveillance for papillary thyroid microcarcinoma (PTMC) is becoming increasingly popular within the global medical community. A key criterion for selecting this strategy is the absence of any signs of lymphogenic or distant metastases. The present study assessed the diagnostic accuracy of molecular genetic markers for predicting the metastatic potential of patients with PTMC. We evaluated the expression levels of 33 molecular genetic markers in cytology samples from 92 patients with PTMC and confirmed histological diagnosis. Among these patients, 32 had metastases to regional cervical lymph nodes. Our findings revealed the upregulated expression of the HMGA2, TIMP1, and FN1 genes, as well as microRNA-146b, in patients with metastatic PTMC. Conversely, we found the downregulated expression of miRNA-7 and -148b in metastatic tumors. In metastatic tumors, significant reductions were observed in DIO1 activity (11-fold), TFF3 gene expression (8-fold), TPO expression (4-fold), and SLC26A7 expression (2.6-fold). All the markers exhibited high sensitivity (84.5–90.6%) in detecting metastatic PTMC, although the specificity proved to be low. The use of molecular markers to predict lymphogenic metastatic spread in patients with PTMC could enhance existing risk grading systems. Such assessments can already be applicable at the preoperative stage.

## Linked entities

- **Genes:** HMGA2 (high mobility group AT-hook 2) [NCBI Gene 8091], TIMP1 (TIMP metallopeptidase inhibitor 1) [NCBI Gene 7076], FN1 (fibronectin 1) [NCBI Gene 2335], DIO1 (iodothyronine deiodinase 1) [NCBI Gene 1733], TFF3 (trefoil factor 3) [NCBI Gene 7033], TPO (thyroid peroxidase) [NCBI Gene 7173], SLC26A7 (solute carrier family 26 member 7) [NCBI Gene 115111]
- **Diseases:** papillary thyroid microcarcinoma (MONDO:0011368)

## Full-text entities

- **Genes:** HMGA2 (high mobility group AT-hook 2) [NCBI Gene 8091] {aka BABL, HMGI-C, HMGIC, LIPO, SRS5, STQTL9}, TIMP1 (TIMP metallopeptidase inhibitor 1) [NCBI Gene 7076] {aka CLGI, EPA, EPO, HCI, TIMP, TIMP-1}, MIR146B (microRNA 146b) [NCBI Gene 574447] {aka MIRN146B, miRNA146B, mir-146b}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, TPO (thyroid peroxidase) [NCBI Gene 7173] {aka MSA, TDH2A, TPX}, SLC26A7 (solute carrier family 26 member 7) [NCBI Gene 115111] {aka SUT2}, TFF3 (trefoil factor 3) [NCBI Gene 7033] {aka ITF, P1B, TFI}, DIO1 (iodothyronine deiodinase 1) [NCBI Gene 1733] {aka 5DI, THMA2, TXDI1}
- **Diseases:** metastatic tumors (MESH:D009369), PTMC (MESH:C563277), metastases (MESH:D009362)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

28 references — full list in the complete paper: https://tomesphere.com/paper/PMC12249573/full.md

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Source: https://tomesphere.com/paper/PMC12249573