Zhou Yusong, Huang Shiwei, Yang Bing, Tan Jing, Zhang Zhun, Liu Wei
Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, China.
Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, China.
Front Pharmacol. 2024 Nov 26;15:1503623. doi: 10.3389/fphar.2024.1503623. eCollection 2024.
Anoikis disrupts the normal apoptotic process in cells, leading to abnormal proliferation and migration, thereby promoting tumor formation and development. However, the role of anoikis in bladder urothelial carcinoma (BLCA) still requires further exploration.
Anoikis-related genes (ARGs) were retrieved from the GeneCards and Harmonizome databases to distinguish various subtypes of BLCA and develop a predictive model for BLCA. The immune microenvironment and enrichment pathways between various subtypes were also analyzed using consensus clustering. Potential medications were screened by utilizing drug sensitivity analysis. and vivo, the character of the independent prognostic gene in BLCA was confirmed through cell studies and mouse xenograft models.
One hundred thirty differentially expressed genes (DEGs) were identified, and nine of them were chosen to construct predictive models that can accurately forecast the prognosis of BLCA patients. K = 2 was correctly identified as the optimal clustering type for BLCA, showing prominent differences in survival rates between the two subgroups. The immune-related functional studies manifested that the two subtypes' immune cell expressions differed. It was verified that RAC3 is an independent prognostic gene for BLCA. RAC3 shows high expression levels in BLCA, as indicated by its consistent mRNA and protein levels across different gene expressions. The functional verification results of RAC3 in BLCA showed that silencing RAC3 can significantly inhibit BLCA cell proliferation, colony formation, and migration. RAC3 knockdown inhibited the growth and migration of BLCA . SB505124 exhibited a significant inhibitory effect on the proliferation of BLCA cells.
Based on the predictive model developed in this study, BLCA patients' prognoses can be accurately predicted. SB505124 could become an important drug in the treatment of BLCA patients. RAC3 is essential in prognosis, immune microenvironment, and malignant behavior of BLCA and . It will also offer the potential for personalized treatment for BLCA patients and generate new research avenues for clinical investigators.
失巢凋亡破坏细胞中的正常凋亡过程，导致异常增殖和迁移，从而促进肿瘤的形成和发展。然而，失巢凋亡在膀胱尿路上皮癌（BLCA）中的作用仍需进一步探索。
从GeneCards和Harmonizome数据库中检索失巢凋亡相关基因（ARGs），以区分BLCA的各种亚型并建立BLCA的预测模型。还使用一致性聚类分析了各亚型之间的免疫微环境和富集途径。通过药物敏感性分析筛选潜在药物。在体外和体内，通过细胞研究和小鼠异种移植模型证实了BLCA中独立预后基因的特征。
鉴定出130个差异表达基因（DEGs），其中9个被选来构建能够准确预测BLCA患者预后的预测模型。K = 2被正确确定为BLCA的最佳聚类类型，两个亚组之间的生存率存在显著差异。免疫相关功能研究表明，两种亚型的免疫细胞表达不同。证实RAC3是BLCA的独立预后基因。RAC3在BLCA中显示出高表达水平，不同基因表达中的mRNA和蛋白质水平一致表明了这一点。RAC3在BLCA中的功能验证结果表明，沉默RAC3可显著抑制BLCA细胞增殖、集落形成和迁移。RAC3敲低抑制了BLCA的生长和迁移。SB505124对BLCA细胞的增殖表现出显著抑制作用。
基于本研究建立的预测模型，可以准确预测BLCA患者的预后。SB505124可能成为治疗BLCA患者的重要药物。RAC3在BLCA的预后、免疫微环境和恶性行为中至关重要。它还将为BLCA患者的个性化治疗提供潜力，并为临床研究人员开辟新的研究途径。
