CST2 promotes cell proliferation and regulates cell cycle by activating Wnt-β-catenin signalling pathway in serous ovarian cancer

Abstract

Background: Cystatin SA (CST2) plays multiple roles in different types of malignant tumours; however, its role in serous ovarian cancer (SOC) remains unclear. Therefore, we aimed to investigate the expression levels, survival outcomes, immune cell infiltration, proliferation, cell cycle, and underlying molecular mechanisms associated with the CST2 signature in SOC.

Methods: The Cancer Genome Atlas database was used to acquire clinical information and CST2 expression profiles from patients with SOC. Wilcoxon rank-sum tests were used to compare CST2 expression levels between SOC and normal ovarian tissues. A prognostic assessment of CST2 was conducted using Cox regression analysis and the Kaplan-Meier method. Differentially expressed genes were identified using functional enrichment analysis. Immune cell infiltration was examined using a single-sample gene set enrichment analysis. Cell cycle characteristics and proliferation were assessed using a colony formation assay, flow cytometry, and a cell counting kit-8 assay. Western blots and quantitative reverse transcription PCR analyses were employed to examine CST2 expressions and related genes involved in the cell cycle and the Wnt-β-catenin signalling pathway.

Results: Our findings revealed significant upregulation of CST2 in SOC, and elevated CST2 expression was correlated with advanced clinicopathological characteristics and unfavourable prognoses. Pathway enrichment analysis highlighted the association between the cell cycle and the Wnt signalling pathway. Moreover, increased CST2 levels were positively correlated with immune cell infiltration. Functionally, CST2 played vital roles in promoting cell proliferation, orchestrating the G1-to-S phase transition, and driving malignant SOC progression through activating the Wnt-β-catenin signalling pathway.

Conclusions: The elevated expression of CST2 may be related to the occurrence and progression of SOC by activating the Wnt-β-catenin pathway. Additionally, our findings suggest that CST2 is a promising novel biomarker with potential applications in therapeutic, prognostic, and diagnostic strategies for SOC.

Keywords: CST2; Wnt-β-catenin signalling pathway; cell cycle; serous ovarian cancer.