TROP2 modulates the progression in papillary thyroid carcinoma.

Background: Tumor-associated calcium signal transducer 2 (TROP2) is over expressed in various kinds of human cancers and plays important roles in the proliferation, invasion and metastasis of tumor cells. However, the expression and molecular mechanism of TROP2 in thyroid papillary carcinoma (PTC) are unclear. Methods: The expressions of TROP2 in PTC and control tissue were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. The proliferation and invasion of PTC cell lines were examined by cell cloning and transwell assays. RNA sequencing analysis and public data analysis were assessed to investigate the potential mechanisms of TROP2 in PTC. Gene correlation analysis was conducted to explore the association between TROP2 and the related gene ISG15 in patients with PTC. Results: The expression of TROP2 was significantly higher in PTC than control. The high expression of TROP2 protein was associated with lymph node metastasis, tumor size and capsular infiltration (P<0.05). SiRNA-mediated TROP2 gene expression silencing can significantly inhibit proliferation and migration of PTC cells. ISG15 decreased in TROP2 siRNA PTC cells and increased in PTC patients significantly. There was a significant correlation between the expression of TROP2 and ISG15 in PTC patients. TROP2 interacted directly with ATP6V1A, CEBPA and SOX5 and then further interacted with the immune genes. TROP2 expression and tumor-infiltrating immune cells were also correlated in thyroid cancer microenvironment. Conclusions: TROP2 promotes the development of PTC. TROP2 expression was correlated with ISG15 and tumor-infiltrating immune cells in thyroid cancer.