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

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 underlyi...

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Main Authors: Xiaohua Wang, Sufen Zhao, Yanwei Guo, Chunhui Wang, Shuyu Han, Xingcha Wang
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Journal of Obstetrics and Gynaecology
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Online Access:https://www.tandfonline.com/doi/10.1080/01443615.2024.2363515
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author Xiaohua Wang
Sufen Zhao
Yanwei Guo
Chunhui Wang
Shuyu Han
Xingcha Wang
author_facet Xiaohua Wang
Sufen Zhao
Yanwei Guo
Chunhui Wang
Shuyu Han
Xingcha Wang
author_sort Xiaohua Wang
collection DOAJ
description 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.
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spelling doaj-art-c87b83b91b2d4e11b9e1424aabe23f1a2025-07-14T18:04:24ZengTaylor & Francis GroupJournal of Obstetrics and Gynaecology0144-36151364-68932024-12-0144110.1080/01443615.2024.2363515CST2 promotes cell proliferation and regulates cell cycle by activating Wnt-β-catenin signalling pathway in serous ovarian cancerXiaohua Wang0Sufen Zhao1Yanwei Guo2Chunhui Wang3Shuyu Han4Xingcha Wang5Department of Gynecology and Obstetrics, The Second Hospital of HeiBei Medical University, Shijiazhuang, ChinaDepartment of Gynecology and Obstetrics, The Second Hospital of HeiBei Medical University, Shijiazhuang, ChinaDepartment of Obstetrics, Affiliated Hospital of Chengde Medical University, Chengde, ChinaDepartment of Gynecology, Affiliated Hospital of Chengde Medical University, Chengde, ChinaDepartment of Gynecology, Affiliated Hospital of Chengde Medical University, Chengde, ChinaDepartment of Gynecology, Affiliated Hospital of Chengde Medical University, Chengde, ChinaBackground 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.https://www.tandfonline.com/doi/10.1080/01443615.2024.2363515CST2serous ovarian cancercell cycleWnt-β-catenin signalling pathway
spellingShingle Xiaohua Wang
Sufen Zhao
Yanwei Guo
Chunhui Wang
Shuyu Han
Xingcha Wang
CST2 promotes cell proliferation and regulates cell cycle by activating Wnt-β-catenin signalling pathway in serous ovarian cancer
Journal of Obstetrics and Gynaecology
CST2
serous ovarian cancer
cell cycle
Wnt-β-catenin signalling pathway
title CST2 promotes cell proliferation and regulates cell cycle by activating Wnt-β-catenin signalling pathway in serous ovarian cancer
title_full CST2 promotes cell proliferation and regulates cell cycle by activating Wnt-β-catenin signalling pathway in serous ovarian cancer
title_fullStr CST2 promotes cell proliferation and regulates cell cycle by activating Wnt-β-catenin signalling pathway in serous ovarian cancer
title_full_unstemmed CST2 promotes cell proliferation and regulates cell cycle by activating Wnt-β-catenin signalling pathway in serous ovarian cancer
title_short CST2 promotes cell proliferation and regulates cell cycle by activating Wnt-β-catenin signalling pathway in serous ovarian cancer
title_sort cst2 promotes cell proliferation and regulates cell cycle by activating wnt β catenin signalling pathway in serous ovarian cancer
topic CST2
serous ovarian cancer
cell cycle
Wnt-β-catenin signalling pathway
url https://www.tandfonline.com/doi/10.1080/01443615.2024.2363515
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