Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
Department of Urology, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, China.
PeerJ. 2023 Aug 16;11:e15670. doi: 10.7717/peerj.15670. eCollection 2023.
Bladder cancer is a clinical and social conundrum due to its high incidence and recurrence rate. It is urgent to find new targets for the diagnosis and treatment of bladder cancer and improve the prognosis and survival rate of bladder cancer patients. We sought a prognosis-related gene, built related models of evaluated bladder cancer and identified the function of the hub gene in bladder cancer.
We downloaded the data of bladder cancer patients from the TCGA database, and used differentially expressed genes (DEGs), copy number variation (CNV) and survival analysis to scan the hub genes associated with prognosis in bladder cancer. Then, multi-factor cox regression was used to obtain the bladder cancer prognosis correlation model. Then, we analyzed the relationship between the expression of hub gene and immune microenvironment of bladder cancer. The relationship between the expression of hub gene and prognosis in bladder cancer patients was verified by immunohistochemistry. Cell proliferation assay and drug sensitivity test were used to verify the inhibition of bladder cancer by targeted inhibitors.
In bladder cancer, we screened seven hub genes () associated with survival. Moreover, the multifactor regression model constructed with hub gene can well distinguish the prognosis of bladder cancer. Hub gene is mostly associated with immune microenvironment. Immunohistochemical results basically confirmed the importance of XPO1 in bladder cancer. Selinexor (an inhibitor of XPO1) could effectively inhibit the proliferation of bladder cancer in the cell proliferation experiments by CCK-8 assays and it could suppress the growth of bladder cancer in mouse bladder cancer model.
In this study, a prognostic model with seven hub genes has provided great help for the prognosis prediction of bladder cancer patients. And is an important target affecting the prognosis of bladder cancer, and inhibition of can effectively inhibit bladder cancer proliferation and growth.
膀胱癌发病率和复发率高，临床诊治较为棘手，是一个临床和社会难题。寻找膀胱癌诊断和治疗的新靶点，改善膀胱癌患者的预后和生存率迫在眉睫。本研究旨在寻找一个与膀胱癌预后相关的基因，构建相关模型并鉴定膀胱癌的核心基因的功能。
从 TCGA 数据库中下载膀胱癌患者的数据，利用差异表达基因（DEGs）、拷贝数变异（CNV）和生存分析扫描与膀胱癌预后相关的枢纽基因。然后，多因素 cox 回归获得膀胱癌预后相关模型。进一步分析枢纽基因与膀胱癌免疫微环境的关系，通过免疫组织化学验证其与膀胱癌患者预后的关系。通过细胞增殖实验和药物敏感性实验验证靶向抑制剂对膀胱癌的抑制作用。
在膀胱癌中，我们筛选出 7 个与生存相关的枢纽基因（）。此外，用枢纽基因构建的多因素回归模型可以很好地区分膀胱癌的预后。枢纽基因与免疫微环境关系密切。免疫组织化学结果基本证实了 XPO1 在膀胱癌中的重要性。CCK-8 检测细胞增殖实验证实，XPO1 抑制剂 selinexor 可有效抑制膀胱癌的增殖，在小鼠膀胱癌模型中可抑制膀胱癌的生长。
本研究构建了一个具有 7 个枢纽基因的预后模型，为膀胱癌患者的预后预测提供了很大的帮助。并且 XPO1 是影响膀胱癌预后的重要靶点，抑制 XPO1 可以有效抑制膀胱癌的增殖和生长。
