Abstract
Thyroid cancer incidence has increased worldwide; however, investigations of thyroid cancer-related factors as potential prognosis markers remain insufficient. Secreted proteins from the cancer secretome are regulators of several molecular mechanisms and are, thereby, ideal candidates for potential markers. We aimed to identify a specific factor for thyroid cancer by analyzing the secretome from normal thyroid cells, papillary thyroid cancer (PTC) cells, and anaplastic thyroid cancer cells using mass spectrometry (MS). Cathepsin B (CTSB) showed highest expression in PTC cells compared to other cell lines, and CTSB levels in tumor samples were higher than that seen in normal tissue. Further, among thyroid cancer patients, increased CTSB expression was related to higher risk of lymph node metastasis (LNM) and advanced N stage. Overexpression of CTSB in thyroid cancer cell lines activated cell migration by increasing the expression of vimentin and Snail, while its siRNA-mediated silencing inhibited cell migration by decreasing vimentin and Snail expression. Mechanistically, CTSB-associated enhanced cell migration and upregulation of vimentin and Snail occurred via increased phosphorylation of p38. As our results suggest that elevated CTSB in thyroid cancer induces the expression of metastatic proteins and thereby leads to LNM, CTSB may be a good and clinically relevant prognostic marker.
Highlights
Thyroid cancer is the most common endocrine-related cancer worldwide, and Surveillance, Epidemiology, and End Results Program data for the last 10 years (2009–2018) reveal that the incidence of thyroid cancer has been stable by about 3% of the new cancer cases
Conditioned media were subjected to two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) to identify differentially expressed proteins (DEPs) and spots with differential intensities were compared to normalized spot intensity of the secretome of epithelial thyroid cell
Analysis of differences in relative expression of the DEPs between papillary and epithelial or anaplastic types (Figure 1A and Figure S1) showed that cathepsin B (CTSB) expression was about 161-times higher in papillary thyroid cancer (PTC) cells compared to epithelial thyroid cells
Summary
Thyroid cancer is the most common endocrine-related cancer worldwide, and Surveillance, Epidemiology, and End Results Program data for the last 10 years (2009–2018) reveal that the incidence of thyroid cancer has been stable by about 3% of the new cancer cases. Even though prognosis in thyroid cancer is excellent and the 5-year survival rate is 98%, the 5-year survival rate drops to 54.9–62.0% in advanced cases [2,3]. As thyroid cancer is rather common and the prognosis is unfavorable in advanced-stage cancer, identification of a useful molecular marker related to thyroid cancer is essential. TERT mutation or apolipoprotein E have reported as a prognostic factor of papillary thyroid cancer (PTC) [6,7]. We thought that the searching for more diverse molecular markers and research methods were needed
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