# Comparative urine proteomic study involving papillary thyroid carcinoma and benign thyroid nodules

**Authors:** Lilong Wei, Rui Xiao, Zhengguang Guo, Pengpeng Wang, Kexin Zhao, Yun Zhou, Wei Sun, Yongtong Cao

PMC · DOI: 10.3389/fonc.2025.1551247 · Frontiers in Oncology · 2025-04-08

## TL;DR

This study compares urine proteins in thyroid cancer and benign nodules to find potential biomarkers for accurate diagnosis.

## Contribution

The study identifies urine proteomic differences and potential biomarkers for distinguishing papillary thyroid carcinoma from benign nodules.

## Key findings

- Papillary thyroid carcinomas showed significant changes in 196 urine proteins compared to benign nodules.
- Semaphorin-6D demonstrated good diagnostic performance with an AUC of 0.763 in ELISA validation.
- Over 100 proteins showed strong diagnostic potential in MS validation with AUC > 0.8.

## Abstract

Accurately differentiating benign and malignant lesions is essential for treatment. We aimed to determine differences in urine proteomics between papillary thyroid carcinomas (PTCs) and benign thyroid nodules (BTNs) and identify biomarkers for the differential diagnosis of these diseases.

We collected 155 specimens. In the discovery group, 30 PTC and 31 BTN specimens were quantitatively compared using liquid chromatography-tandem mass spectrometry (MS). The diagnostic value of each significantly altered protein was calculated in the MS validation comprising 11 PTC and 10 BTN samples. Ultimately, 36 BTN and 37 PTC specimens were used for ELISA validation.

Overall, 2,479 proteins were used for quantitative analysis. Compared with benign nodules, papillary carcinomas showed significant increases and decreases in the levels of 169 and 27 proteins, respectively. Neck and thyroid tumors were enriched in the disease or function category. More than 100 proteins showed good performance in the area under the receiver operating characteristic curve (>0.8) upon MS validation. Semaphorin-6D showed good performance (AUC = 0.763) in ELISA validation. Urine proteomics is an effective diagnostic tool for distinguishing benign and malignant thyroid diseases. Semaphorin-6D may serve as a disease marker for large-scale validation and use. Additionally, this study identified potential biomarkers that warrant further investigation.

## Linked entities

- **Diseases:** papillary thyroid carcinoma (MONDO:0005075)

## Full-text entities

- **Genes:** SEMA6D (semaphorin 6D) [NCBI Gene 80031]
- **Diseases:** thyroid diseases (MESH:D013959), BTNs (MESH:D016606), PTC (MESH:D000077273), thyroid tumors (MESH:D013964), Neck (MESH:D006258), papillary carcinomas (MESH:D002291)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12011787/full.md

## References

37 references — full list in the complete paper: https://tomesphere.com/paper/PMC12011787/full.md

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Source: https://tomesphere.com/paper/PMC12011787