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

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. 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. 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. 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. Serous ovarian cancer is a type of gynecological malignant tumour with high mortality rates. Understanding this disease is crucial for improving treatments and enhancing patient survival. In our study, we investigated a protein called CST2 and its role in serous ovarian cancer. We found that CST2 levels vary among patients and are associated with the progression of cancer and the prognosis of the patient, which could be valuable for future diagnosis and treatment strategies. However, further research is needed to validate these findings. Despite its limitations, our findings suggest that CST2 holds promise as a potential biomarker for detecting serous ovarian cancer and as a therapeutic target in the management of patients with this type of cancer.

半胱氨酸蛋白酶抑制剂SA（Cystatin SA, CST2）在多种恶性肿瘤中发挥多重生物学功能，但其在浆液性卵巢癌（serous ovarian cancer, SOC）中的作用尚未明确。为此，本研究旨在探讨CST2表达特征在SOC中的表达水平、患者生存结局、免疫细胞浸润情况、细胞增殖能力、细胞周期特征及潜在分子机制。我们从癌症基因组图谱（The Cancer Genome Atlas, TCGA）数据库中获取SOC患者的临床信息与CST2表达谱数据。采用Wilcoxon秩和检验比较SOC组织与正常卵巢组织的CST2表达水平差异。通过Cox回归分析与Kaplan-Meier法开展CST2的预后评估。利用功能富集分析筛选差异表达基因。采用单样本基因集富集分析检测免疫细胞浸润状态。通过集落形成实验、流式细胞术及细胞计数试剂盒-8（cell counting kit-8, CCK-8）实验评估细胞周期特征与细胞增殖能力。采用蛋白质印迹法（Western blot）与定量逆转录聚合酶链反应（quantitative reverse transcription PCR, qRT-PCR）检测CST2的表达水平，以及参与细胞周期与Wnt-β-连环蛋白信号通路的相关基因表达情况。本研究结果显示，CST2在SOC组织中显著上调，且CST2高表达与晚期临床病理特征及不良预后显著相关。通路富集分析揭示细胞周期与Wnt信号通路存在密切关联。此外，CST2表达水平升高与免疫细胞浸润呈正相关。功能实验表明，CST2可通过激活Wnt-β-连环蛋白信号通路，在促进细胞增殖、调控G1期向S期转化及推动SOC恶性进展中发挥关键作用。CST2表达上调可能通过激活Wnt-β-连环蛋白通路参与SOC的发生与疾病进展。此外，本研究结果提示CST2是一种极具潜力的新型生物标志物，在SOC的诊断、预后评估及治疗策略中具备潜在应用价值。浆液性卵巢癌是一类死亡率较高的妇科恶性肿瘤，深入解析该疾病对于优化治疗方案、改善患者生存结局至关重要。本研究聚焦于CST2蛋白，探讨其在浆液性卵巢癌中的作用。研究发现，不同患者的CST2表达水平存在差异，且与癌症进展及患者预后密切相关，这一发现可为未来的诊断与治疗策略提供重要参考。不过，仍需开展进一步研究以验证本研究结果。尽管本研究存在一定局限性，但其结果表明CST2有望成为检测浆液性卵巢癌的潜在生物标志物，同时可作为该类癌症患者临床管理的潜在治疗靶点。