Yao Jiahao, Zhang Hongyu, Gu Qiang, Sun Xiaoyang, Li Lang, Wang Xuefeng
Department of Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Departmentof Neurosurgery, Harbin Medical University Cancer Hospital, Harbin, China.
BMC Cancer. 2025 Jul 1;25(1):1079. doi: 10.1186/s12885-025-14441-0.
The present study aimed to construct a tumor risk prognosis model and explore the role of PSMA5 in glioblastoma (GBM), focusing on its association with cellular senescence and its potential as both a prognostic biomarker and therapeutic target.
Data from the DepMap and Cellage databases were integrated to develop a risk prognosis model, and were refined and evaluated using LASSO and Cox regression analyses. PSMA5 expression in GBM was analyzed via bioinformatics methods and validated in cell lines. Functional experiments using U87 and U251 cells subjected to PSMA5 overexpression and knockdown were conducted to assess changes in proliferation, senescence, cell cycle, DNA damage and associated protein expression. Additionally, a subcutaneous tumor model in immunodeficient mice was used to evaluate tumor growth and analyze tissue characteristics.
The model identified 5 key genes and demonstrated strong predictive accuracy, with high-risk patients exhibiting significantly shorter survival times. PSMA5 expression was notably elevated in GBM tissues and cell lines compared with normal controls and associated with clinical features. Functional assays revealed that PSMA5 regulates GBM cell proliferation, invasion and migration, while its knockdown induced cellular senescence, characterized by increased β-galactosidase activity, disrupted cell cycle progression and DNA damage. In vivo studies confirmed that PSMA5 overexpression significantly accelerated tumor growth and was widely distributed within tumor tissues.
The proposed model is reliable, and PSMA5 plays a critical role in GBM progression by influencing tumor cell behavior and promoting growth. As both a prognostic biomarker and a therapeutic target, PSMA5 offers valuable insights for advancing GBM research and treatment strategies.
本研究旨在构建一个肿瘤风险预后模型，探讨PSMA5在胶质母细胞瘤（GBM）中的作用，重点关注其与细胞衰老的关联以及作为预后生物标志物和治疗靶点的潜力。
整合来自DepMap和Cellage数据库的数据以开发风险预后模型，并使用LASSO和Cox回归分析进行优化和评估。通过生物信息学方法分析GBM中PSMA5的表达，并在细胞系中进行验证。对过表达和敲低PSMA5的U87和U251细胞进行功能实验，以评估增殖、衰老、细胞周期、DNA损伤及相关蛋白表达的变化。此外，利用免疫缺陷小鼠皮下肿瘤模型评估肿瘤生长并分析组织特征。
该模型识别出5个关键基因，具有很强的预测准确性，高危患者的生存时间明显缩短。与正常对照相比，GBM组织和细胞系中PSMA5表达显著升高，并与临床特征相关。功能分析表明，PSMA5调节GBM细胞的增殖、侵袭和迁移，而敲低PSMA5可诱导细胞衰老，表现为β-半乳糖苷酶活性增加、细胞周期进程紊乱和DNA损伤。体内研究证实，PSMA5过表达显著加速肿瘤生长，且在肿瘤组织中广泛分布。
所提出的模型可靠，PSMA5通过影响肿瘤细胞行为和促进生长在GBM进展中起关键作用。作为预后生物标志物和治疗靶点，PSMA5为推进GBM研究和治疗策略提供了有价值的见解。
