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Peer-reviewedCC BY 4.0Frontiers in Endocrinology

Ultrasound features for identifying cancer-associated fibroblasts expression in papillary thyroid carcinoma

  • Tingting Li1
  • Jiping Xue1
  • Xueting Li2
  • Changjuan Hao1
  • Zhexia Zhao1
  1. 1Department of Ultrasound, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital
  2. 2Department of Pathology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital
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Abstract

Background: Cancer-associated fibroblasts (CAFs) play a critical role in tumor proliferation, invasion, and metastasis, and are considered an important indicator of aggressiveness in papillary thyroid carcinoma (PTC). However, non-invasive assessment of CAFs activation in vivo remains challenging. This study aimed to investigate the association between preoperative ultrasound (US) features and the expression levels of CAFs-related markers in PTC, and to assess the utility of US parameters for identifying high CAFs expression.

Methods: This retrospective study included 158 patients with pathologically confirmed PTC who underwent preoperative conventional US and shear wave elastography (SWE). Immunohistochemical staining for fibroblast activation protein (FAP) and α-smooth muscle actin (α-SMA) was performed as markers of CAFs. US parameters were compared between the low and high CAFs expression groups. Correlations between the US parameters and FAP/α-SMA immunoreactivity scores (IRS) were assessed using Spearman’s correlation analysis. Multivariate logistic regression analysis was conducted to identify independent US factors associated with high CAFs expression, and their diagnostic performance was evaluated using receiver operating characteristic (ROC) curves.

Results: Significant differences were observed in tumor size, suspected extrathyroidal extension, Emax, Emean, and ESD between low and high expression groups of FAP and α-SMA (all P < 0.001). Blood flow grade also differed significantly between FAP expression groups ( P < 0.001). The IRS of both FAP and α-SMA correlated most strongly with Emax (r = 0.555 and 0.575, respectively; both P < 0.001).

Multivariate analysis identified blood flow grade 2–3 (OR = 2.513, 95% CI: 1.049–6.025, P = 0.039) and Emax (OR = 1.038, 95% CI: 1.003–1.074, P = 0.033) were independently associated with high FAP expression, whereas only Emax (OR = 1.048, 95% CI: 1.012–1.085, P = 0.009) was independently associated with high α-SMA expression. Emax showed good diagnostic performance for both FAP (AUC = 0.799) and α-SMA (AUC = 0.819). Adding blood flow grade to Emax did not significantly improve AUC for identifying high FAP expression (0.826 vs. 0.799, P = 0.564).

Conclusion: US parameters, particularly Emax, are valuable for non-invasively assessing CAFs activation in PTC, which could help to guide individualized preoperative clinical decision-making.

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Cite

BibTeXRIS
BibTeX
@article{li2026ultrasound,
  title = {{Ultrasound features for identifying cancer-associated fibroblasts expression in papillary thyroid carcinoma}},
  author = {Tingting Li and Jiping Xue and Xueting Li and Changjuan Hao and Zhexia Zhao},
  journal = {Frontiers in Endocrinology},
  year = {2026},
  month = oct,
  doi = {10.3389/fendo.2026.1914939},
  url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1914939/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Ultrasound features for identifying cancer-associated fibroblasts expression in papillary thyroid carcinoma
AU  - Tingting Li
AU  - Jiping Xue
AU  - Xueting Li
AU  - Changjuan Hao
AU  - Zhexia Zhao
PY  - 2026
DA  - 2026/10/19
JO  - Frontiers in Endocrinology
DO  - 10.3389/fendo.2026.1914939
UR  - https://www.frontiersin.org/articles/10.3389/fendo.2026.1914939/full
AB  - Background: Cancer-associated fibroblasts (CAFs) play a critical role in tumor proliferation, invasion, and metastasis, and are considered an important indicator of aggressiveness in papillary thyroid carcinoma (PTC). However, non-invasive assessment of CAFs activation in vivo remains challenging. This study aimed to investigate the association between preoperative ultrasound (US) features and the expression levels of CAFs-related markers in PTC, and to assess the utility of US parameters for identifying high CAFs expression.  Methods: This retrospective study included 158 patients with pathologically confirmed PTC who underwent preoperative conventional US and shear wave elastography (SWE). Immunohistochemical staining for fibroblast activation protein (FAP) and α-smooth muscle actin (α-SMA) was performed as markers of CAFs. US parameters were compared between the low and high CAFs expression groups. Correlations between the US parameters and FAP/α-SMA immunoreactivity scores (IRS) were assessed using Spearman’s correlation analysis. Multivariate logistic regression analysis was conducted to identify independent US factors associated with high CAFs expression, and their diagnostic performance was evaluated using receiver operating characteristic (ROC) curves.  Results: Significant differences were observed in tumor size, suspected extrathyroidal extension, Emax, Emean, and ESD between low and high expression groups of FAP and α-SMA (all P < 0.001). Blood flow grade also differed significantly between FAP expression groups ( P < 0.001). The IRS of both FAP and α-SMA correlated most strongly with Emax (r = 0.555 and 0.575, respectively; both P < 0.001).  Multivariate analysis identified blood flow grade 2–3 (OR = 2.513, 95% CI: 1.049–6.025, P = 0.039) and Emax (OR = 1.038, 95% CI: 1.003–1.074, P = 0.033) were independently associated with high FAP expression, whereas only Emax (OR = 1.048, 95% CI: 1.012–1.085, P = 0.009) was independently associated with high α-SMA expression. Emax showed good diagnostic performance for both FAP (AUC = 0.799) and α-SMA (AUC = 0.819). Adding blood flow grade to Emax did not significantly improve AUC for identifying high FAP expression (0.826 vs. 0.799, P = 0.564).  Conclusion: US parameters, particularly Emax, are valuable for non-invasively assessing CAFs activation in PTC, which could help to guide individualized preoperative clinical decision-making.
SN  - 1664-2392
ER  -