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.

Keywords: Cell proliferation; Clinical prognosis; Invasion; Migration; Ovarian clear cell carcinoma; TRPS1.

Fig. 1

TRPS1 was highly expressed in ovarian clear cell carcinoma tissues. A: TRPS1 expression was significantly higher in ovarian clear cell carcinoma tissues compared to normal ovarian tissues (1.66 ± 1.96 vs. 0.25 ± 0.44, p = 0.0018). B: Immunohistochemical analysis of TRPS1 expression in normal ovarian tissue and ovarian clear cell carcinoma (×400). (I) TRPS1 is minimally expressed in normal ovarian tissue; (II) TRPS1 shows a negative expression profile in OCCC; (III) TRPS1 exhibits a positive expression profile in OCCC

Fig. 2

Kaplan-Meier survival curves illustrating the impact of TRPS1 expression on the prognosis of OCCC patients. A: High TRPS1 expression is associated with shorter overall survival and worse prognosis. B: High TRPS1 expression is associated with shorter progression-free survival and worse prognosis

Fig. 3

TRPS1 expression in ovarian clear cell carcinoma cells. A-B: Western blot (WB) and real-time quantitative PCR (RT-qPCR) were used to measure TRPS1 expression in TOV21G and ES-2 cells. C-D: TRPS1 overexpression efficiency in ES-2 cells was confirmed using RT-qPCR and Western blot after transfection with the TRPS1 overexpression plasmid. E-F: Knockdown efficiency in TOV21G cells transfected with TRPS1-siRNA1 or TRPS1-siRNA2 was validated by RT-qPCR and Western blot. (*p < 0.05, **p < 0.01, ***p < 0.001)

Fig. 4

TRPS1 promotes cell proliferation. A-C: CCK-8 assay was used to assess the effect of TRPS1 on cell proliferation. B-D: Plate colony formation assay was conducted to evaluate the impact of TRPS1 on the colony-forming ability of OCCC cells

Fig. 5

TRPS1 enhances cell invasion and migration in vitro. A: Transwell assay confirmed the reduced invasive ability of TOV21G cells following TRPS1 knockdown. B: Transwell assay confirmed the increased invasive ability of ES-2 cells after TRPS1 overexpression. C: Knockdown of TRPS1 impaired the migratory ability of TOV21G cells. D: Overexpression of TRPS1 enhanced the migratory ability of ES-2 cells

Fig. 6

TRPS1 promotes cell invasion and migration. A-B: Western blot analysis was performed to assess changes in the expression levels of N-cadherin, E-cadherin, MMP2, and MMP9 after modulation of TRPS1 expression, with GAPDH used as an internal control