Li Bingxin, Yao Tianze, Zhang Min, Yu Jiaxuan, Xie Jiping, Wan Yi, Ge Yuchuan, Sun Guangze, Yao Yongqiang
Department of Breastplate Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, Liaoning Province, China.
Jinzhou Medical University, Jinzhou, 121000, Liaoning Province, China.
Sci Rep. 2025 Apr 29;15(1):15052. doi: 10.1038/s41598-025-96542-1.
PDZ-binding kinase/T-lymphokine-activated killer-cell-originated protein kinase (PBK/TOPK) is a serine-threonine protein kinase. This study aimed to investigate the expression pattern, prognostic significance, and relationship with tumor immune infiltration of PBK/TOPK in breast cancer through bioinformatics analyses and immunohistochemistry (IHC), providing insights for individualized treatment and immunotherapy strategies. PBK/TOPK expression and its correlation with clinicopathological features were analyzed using TIMER, UALCAN, and TCGA databases. Prognostic value was assessed via Kaplan-Meier plotter and bc-GenExMiner. Variants of the PBK/TOPK gene and their prognostic implications were explored using cBioPortal. Enrichment analysis in R identified signaling pathways linked to PBK/TOPK. The relationships between PBK/TOPK, tumor-infiltrating lymphocytes (TILs), and immune cell markers were evaluated using TIMER and TISIDB. IHC experiments validated PBK/TOPK expression in tumor samples and its association with prognosis. Meanwhile, IHC also further confirmed the correlation between PBK/TOPK and CD4 and CD8 T cells infiltration, as well as the relationship between T cells and breast cancer prognosis. PBK/TOPK was significantly overexpressed in breast cancer tissues compared to normal tissues and correlated with clinicopathological features, including tumor size and lymph node stage. High expression of PBK/TOPK was associated with poor prognosis. While breast cancer subtypes exhibited different PBK/TOPK gene variants, these variants did not influence prognosis. PBK/TOPK is involved in cell meiosis, cytoskeletal motility, and pathways such as FoxO and p53. It is associated with immune infiltration and is differentially expressed in breast cancer subtypes and correlates with TILs and immune cell markers. IHC confirms that PBK/TOPK expression positively correlates with CD4 T and CD8 T cells infiltration. CD4 T cells were positively associated with the prognosis of triple-negative breast cancer. PBK/TOPK is overexpressed in breast cancer tissues, and high expression levels are associated with poor patient prognosis. Additionally, PBK/TOPK is linked to immune infiltration in breast cancer, positively correlating with CD4 and CD8 T cells infiltration, suggesting a new avenue for immunotherapy research in breast cancer.
PDZ结合激酶/T淋巴细胞激活的杀伤细胞源蛋白激酶(PBK/TOPK)是一种丝氨酸-苏氨酸蛋白激酶。本研究旨在通过生物信息学分析和免疫组织化学(IHC)研究PBK/TOPK在乳腺癌中的表达模式、预后意义及其与肿瘤免疫浸润的关系,为个体化治疗和免疫治疗策略提供见解。使用TIMER、UALCAN和TCGA数据库分析PBK/TOPK的表达及其与临床病理特征的相关性。通过Kaplan-Meier绘图仪和bc-GenExMiner评估预后价值。使用cBioPortal探索PBK/TOPK基因的变异及其预后意义。R中的富集分析确定了与PBK/TOPK相关的信号通路。使用TIMER和TISIDB评估PBK/TOPK、肿瘤浸润淋巴细胞(TILs)和免疫细胞标志物之间的关系。IHC实验验证了肿瘤样本中PBK/TOPK的表达及其与预后的关联。同时,IHC还进一步证实了PBK/TOPK与CD4和CD8 T细胞浸润之间的相关性,以及T细胞与乳腺癌预后之间的关系。与正常组织相比,PBK/TOPK在乳腺癌组织中显著过表达,且与包括肿瘤大小和淋巴结分期在内的临床病理特征相关。PBK/TOPK的高表达与不良预后相关。虽然乳腺癌亚型表现出不同的PBK/TOPK基因变异,但这些变异并不影响预后。PBK/TOPK参与细胞减数分裂、细胞骨架运动以及FoxO和p53等通路。它与免疫浸润相关,在乳腺癌亚型中差异表达,与TILs和免疫细胞标志物相关。IHC证实PBK/TOPK表达与CD4 T和CD8 T细胞浸润呈正相关。CD4 T细胞与三阴性乳腺癌的预后呈正相关。PBK/TOPK在乳腺癌组织中过表达,高表达水平与患者不良预后相关。此外,PBK/TOPK与乳腺癌中的免疫浸润相关,与CD4和CD8 T细胞浸润呈正相关,为乳腺癌免疫治疗研究提供了新途径。