Upregulation of TRPS1 promotes proliferation, migration, and invasion in ovarian clear cell carcinoma and correlates with poor patient prognosis.

Abstract

Objective: Tricho-rhino-phalangeal syndrome-1 (TRPS1), an atypical GATA transcription factor, plays a critical role in diverse physiological and pathological processes and holds potential as a biomarker for diseases and targeted tumor therapies. This study explores TRPS1 expression in ovarian clear cell carcinoma (OCCC), its correlation with patient prognosis, and its involvement in OCCC pathogenesis.

Research objectives and methods: To investigate TRPS1 expression, we analyzed ovarian tissues from 50 OCCC patients and 25 normal tissues (from patients with uterine leiomyoma) via immunohistochemistry. Statistical methods, including Chi-square tests, Kaplan-Meier survival analysis, and Cox regression, were employed to evaluate the correlation between TRPS1 expression and clinicopathological parameters. In OCCC cell lines (TOV21G and ES-2), TRPS1 expression was quantified using qRT-PCR and Western blot. Functional studies were conducted by silencing TRPS1 in TOV21G cells with small interfering RNA and inducing overexpression in ES-2 cells using a plasmid. Cellular proliferation and migration were assessed through CCK-8, colony formation, and Transwell assays. Finally, Western blot analysis was performed to investigate the link between TRPS1 and EMT-related molecular pathways.

Results: TRPS1 protein expression was significantly higher in OCCC tissues compared to normal tissues and was positively associated with lymph node metastasis and advanced clinical stage. High TRPS1 expression was linked to shorter overall and recurrence-free survival in OCCC patients. In vitro, TRPS1 knockdown suppressed cell proliferation, migration, and invasion, accompanied by reduced levels of invasion-promoting proteins (N-cadherin, MMP2, MMP9) and increased expression of the invasion-inhibiting protein E-cadherin. Conversely, TRPS1 overexpression promoted the expression of invasion-promoting proteins.

Conclusions: TRPS1 is overexpressed in OCCC and is associated with poor prognosis, serving as an independent predictor of patient outcomes. Its elevated expression enhances OCCC cell proliferation, migration, and invasion by regulating proteins involved in the epithelial-to-mesenchymal transition (EMT) pathway. These findings highlight TRPS1 as a critical player in OCCC pathogenesis and a potential biomarker and therapeutic target for disease management.