Quantitative proteomics analysis of papillary thyroid carcinoma reveals protein S, clusterin, and leucine-rich α-2-glycoprotein 1 as potential prognostic protein biomarkers

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. The primary challenge is identifying patient subgroups with PTC and choosing the most effective treatment approach. To explore the differentially expressed proteins (DEPs) between high and low recurrent-risk PTCs, we collected 15 tissues comprising high (n = 7) and low (n = 8) recurrent-risk groups from PTC. The samples were detected by tandem mass tag labeling proteomics. Using The Cancer Genome Atlas data on thyroid cancer, prognosis-related DEPs were identified. Furthermore, an immunohistochemistry stain of 53 cases of PTC tumors was adopted to validate the relation of potential biomarkers with prognosis. We identified 8958 proteins from the 15 samples, with 95 DEPs obtained by comparing high and low recurrent-risk groups, including 38 upregulated and 57 downregulated proteins. Three downregulated proteins (protein S [PROS1], clusterin [CLU], and leucine-rich α-2-glycoprotein 1 [LRG1]) were found to be significantly associated with poor overall survival in thyroid cancer using differential analysis and Kaplan-Meier survival analysis. Immunohistochemistry results showed low or moderated expressions of PROS1, CLU, and LRG1 were significantly associated with high-risk clinicopathologic characteristics of PTC. PTC patients with higher expression of PROS1, CLU, and LRG1 had better progression-free survival than those with low or moderate expression. Our study identified PROS1, CLU, and LRG1 as novel prognostic biomarkers in PTC.