CST2 通过激活浆液性卵巢癌细胞中的 Wnt-β-连环蛋白信号通路促进细胞增殖并调节细胞周期。
CST2 promotes cell proliferation and regulates cell cycle by activating Wnt-β-catenin signalling pathway in serous ovarian cancer.
机构信息
Department of Gynecology and Obstetrics, The Second Hospital of HeiBei Medical University, Shijiazhuang, China.
Department of Gynecology, Affiliated Hospital of Chengde Medical University, Chengde, China.
出版信息
J Obstet Gynaecol. 2024 Dec;44(1):2363515. doi: 10.1080/01443615.2024.2363515. Epub 2024 Jun 12.
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.
背景
半胱氨酸蛋白酶抑制剂 SA（CST2）在多种恶性肿瘤中发挥多种作用；然而，其在浆液性卵巢癌（SOC）中的作用尚不清楚。因此，我们旨在研究 CST2 特征在 SOC 中与表达水平、生存结局、免疫细胞浸润、增殖、细胞周期和潜在分子机制相关的表达水平、生存结局、免疫细胞浸润、增殖、细胞周期和潜在分子机制。
方法
使用癌症基因组图谱数据库从 SOC 患者中获取临床信息和 CST2 表达谱。使用 Wilcoxon 秩和检验比较 SOC 和正常卵巢组织中 CST2 的表达水平。使用 Cox 回归分析和 Kaplan-Meier 方法对 CST2 进行预后评估。使用功能富集分析鉴定差异表达基因。使用单样本基因集富集分析检查免疫细胞浸润。使用集落形成试验、流式细胞术和细胞计数试剂盒-8 测定评估细胞周期特征和增殖。使用 Western blot 和定量逆转录 PCR 分析检测 CST2 表达和涉及细胞周期和 Wnt-β-连环蛋白信号通路的相关基因。
结果
我们的研究结果表明，SOC 中 CST2 的表达显著上调，CST2 表达升高与先进的临床病理特征和不良预后相关。途径富集分析突出了细胞周期与 Wnt 信号通路之间的关联。此外，CST2 水平的升高与免疫细胞浸润呈正相关。功能上，CST2 通过激活 Wnt-β-连环蛋白信号通路，在促进细胞增殖、协调 G1 至 S 期转变以及驱动恶性 SOC 进展方面发挥重要作用。
结论
CST2 的高表达可能通过激活 Wnt-β-连环蛋白通路与 SOC 的发生和进展有关。此外，我们的研究结果表明，CST2 是一种有前途的新型生物标志物，可能在 SOC 的治疗、预后和诊断策略中有应用前景。
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