南方医科大学学报 ›› 2025, Vol. 45 ›› Issue (10): 2210-2222.doi: 10.12122/j.issn.1673-4254.2025.10.17

• • 上一篇    

PDZ结合激酶作为胰腺癌潜在预后标志物:从泛癌分析到胰腺癌验证

王锦帼1(), 马扬2, 李赵鑫3, 何丽妃3, 黄英泽4(), 范晓明5()   

  1. 1.桂林医科大学,公共卫生学院,广西 桂林 541004
    2.桂林医科大学,基础医学院,广西 桂林 541004
    5.桂林医科大学,广西肿瘤免疫与微环境调控重点实验室,广西 桂林 541004
    3.桂林医科大学附属医院放射肿瘤科,广西 桂林 541001
    4.桂林医科大学附属临床检验中心,广西 桂林 541001
  • 收稿日期:2025-04-23 出版日期:2025-10-20 发布日期:2025-10-24
  • 通讯作者: 黄英泽,范晓明 E-mail:wangjinguo401@alu.glmc.edu.cn;youshxicun@glmc.edu.cn;fanxiaom1987@ glmc.edu.cn
  • 作者简介:王锦帼,硕士,E-mail: wangjinguo401@alu.glmc.edu.cn
  • 基金资助:
    广西自然科学基金(2023JJA141287)

PDZ-binding kinase as a prognostic biomarker for pancreatic cancer: a pan-cancer analysis and validation in pancreatic adenocarcinoma cells

Jinguo WANG1(), Yang MA2, Zhaoxin LI3, Lifei HE3, Yingze HUANG4(), Xiaoming FAN5()   

  1. 1.School of Public Health, Guilin Medical University, Guilin 541004, China
    2.School of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China
    5.Guangxi Key Laboratory of Tumor Immunity and Microenvironment Regulation, Guilin Medical University, Guilin 541004, China
    3.Department of Radiation Oncology, Affiliated Hospital of Guilin Medical University, Guilin 541001, China
    4.Affiliated Clinical Laboratory Center of Guilin Medical University, Guilin 541001, China
  • Received:2025-04-23 Online:2025-10-20 Published:2025-10-24
  • Contact: Yingze HUANG, Xiaoming FAN E-mail:wangjinguo401@alu.glmc.edu.cn;youshxicun@glmc.edu.cn;fanxiaom1987@ glmc.edu.cn

摘要:

目的 研究PDZ结合激酶(PBK)在胰腺癌(包含33种癌症类型)中的表达及其预后意义,并探索其作为治疗靶点的潜力。 方法 采用TCGA、GEO和CPTAC数据库对33种肿瘤组织中PBK的表达进行分析,采用RT-PCR、Western blotting对胰腺癌临床标本及细胞中PBK的表达进行分析。通过生存分析、Cox回归分析、ROC曲线分析和临床相关性研究评估其对胰腺癌的诊断和预后价值。通过基因富集和免疫相关性分析来探讨PBK在肿瘤微环境中的潜在作用。通过对GDSC及CTRP的数据集的分析,研究PBK表达与药物敏感性的关系。通过慢病毒沉默方法建立沉默PBK的胰腺癌BXPC-3的稳定细胞系。采用CCK-8、细胞克隆、transwell实验检测沉默PBK后,对胰腺癌细胞增殖、迁移和侵袭的影响。采用免疫共沉淀和Western blotting研究PBK与非SMC凝聚素II复合亚基G2(NCAPG2)的相互作用。 结果 PBK在多种癌症组织及胰腺癌中过表达(P<0.05),具有较高的诊断价值,PBK的高表达与不良预后相关(P<0.05)。PBK的高表达还与免疫浸润和肿瘤微环境特征的改变有关。PBK高表达对MEK抑制剂(曲美替尼)及EGFR抑制剂(阿法替尼)的敏感性呈正相关,但对Bcl-2抑制剂(TW37)及氯硝柳胺的敏感性呈负相关(P<0.05)。进一步敲低PBK抑制了NCAPG2的表达,且抑制了胰腺癌细胞增殖、迁移和侵袭(P<0.05)。免疫共沉淀显示PBK能够与NCAPG2直接结合。 结论 PBK是胰腺癌的关键调节因子,并与NCAPG2相互作用,促进胰腺癌的进展。它可能作为胰腺癌的潜在生物标志物和治疗靶点,同时为泛癌症研究提供新的见解。

关键词: PDZ结合激酶, 泛癌分析, 胰腺癌, 免疫浸润, 生物标志物, NCAPG2

Abstract:

Objective To investigate the prognostic significance of PDZ-binding kinase (PBK) in pan-cancer and its potential as a therapeutic target for pancreatic cancer. Methods PBK expression levels were investigated in 33 cancer types based on data from TCGA, GEO and CPTAC databases. RT-PCR and Western blotting were employed to examine PBK expression in clinical pancreatic cancer specimens and cell lines. The diagnostic and prognostic value of PBK in pancreatic cancer was evaluated using survival analysis, Cox regression analysis, ROC curve analysis, and clinical correlation studies. Gene enrichment and immune correlation analyses were conducted to explore the potential role of PBK in tumor microenvironment, and its correlation with drug sensitivity was investigated using GDSC and CTRP datasets. In pancreatic cancer BXPC-3 cells, the effects of lentivirus-mediated PBK knockdown on cell proliferation, migration, and invasion were examined using CCK-8, colony formation, and Transwell assays. The interaction between PBK and non-SMC condensin II complex subunit G2 (NCAPG2) was analyzed using co-immunoprecipitation and Western blotting. Results PBK was overexpressed in multiple cancer types, including pancreatic cancer. A high PBK expression was associated with a poor prognosis of the patients and correlated with immune infiltration and alterations in the tumor microenvironment. Elevated PBK expression was positively correlated with the sensitivity to MEK inhibitors (Trametinib) and EGFR inhibitors (Afatinib) but negatively with the sensitivity to Bcl-2 inhibitors (TW37) and niclosamide. In BXPC-3 cells, PBK knockdown significantly suppressed NCAPG2 expression and inhibited cell proliferation, migration, and invasion. Co-immunoprecipitation confirmed a direct binding between PBK and NCAPG2. Conclusion PBK is a key regulator of pancreatic cancer and interacts with NCAPG2 to promote tumor progression, suggesting its value as a potential biomarker and therapeutic target for pancreatic cancer.

Key words: PDZ-binding kinase, pan-cancer analysis, pancreatic cancer, immune invasion, biomarker, NCAPG2