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

Introduction: 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. Methods: 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. Results and discussion: 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.