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

Abstract

Background 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. Results To explore the differently 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 TCGA (The Cancer Genome Atlas) data on thyroid cancer, prognosis-related DEPs were identified. Furthermore, an immunohistochemistry (IHC) stain of 53 cases of PTC tumors was adopted to validate the relation of potential biomarkers with prognosis. We identified 8,958 proteins from the 15 samples, with 95 DEPs obtained by comparing high and low-recurrent-risk groups, including 38 up-regulated and 57 down-regulated proteins. Three down-regulated 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. IHC 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. Conclusions Our study identified PROS1, CLU, and LRG1 as novel prognostic biomarkers in PTC.