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中国癌症防治杂志

中国癌症防治杂志 ›› 2025, Vol. 17 ›› Issue (2): 188-195.doi: 10.3969/j.issn.1674-5671.2025.02.09

• 论著 • 上一篇    下一篇

HSP90AB1在卵巢癌顺铂耐药形成过程中表达量的变化及其意义

  

  1. 广西医科大学附属肿瘤医院实验研究部；溶瘤纳米体系开发广西高校工程研究中心；区域性高发肿瘤早期防治研究教育部重点实验室（广西医科大学）；广西医科大学第一附属医院肿瘤内科
  • 出版日期:2025-04-25 发布日期:2025-05-15
  • 通讯作者: 石丽君,E-mail：shilijun512@126.com;王琪, E-mail：wangqi@stu.gxmu.edu.cn
  • 基金资助:
    国家自然科学基金项目（82102962；82260484）；广西中青年教师能力提升项目（2021KY0082）；区域性高发肿瘤早期防治研究教育部重点实验室自主研究基金项目(GKE?ZZ202016)

Alterations of HSP90AB1 expression in ovarian cancer during cisplatin resistance and its clinical significance

  • Online:2025-04-25 Published:2025-05-15
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摘要： 目的 探讨热休克蛋白90α家族B类成员1（heat shock protein 90 kDa alpha, class B,member 1，HSP90AB1）对卵巢癌患者预后及顺铂耐药的影响。方法 采用时间序列分析法分析裸鼠皮下移植瘤模型在铂耐药过程中mRNA、miRNA 及蛋白质的变化，筛选出潜在耐药关键基因HSP90AB1，Western blot检测皮下移植瘤组织中HSP90AB1表达量的变化，分析210例TCGA数据库中卵巢癌患者的临床预后数据与顺铂耐药的关系。利用RNA干扰技术敲低SKOV3细胞中HSP90AB1基因的表达，CCK⁃8 实验计算细胞的顺铂半数抑制浓度（half⁃maximal inhibitory concentration，IC50）；流式细胞术检测细胞的凋亡情况。结果 共筛选出14个上调及32个下调的基因及蛋白质，与miRNA存在靶向关系，通过蛋白⁃蛋白互作分析，选择得分最高的基因簇的核心基因HSP90AB1进行分析。Western blot证实在铂耐药发生过程中，移植瘤组织中的HSP90AB1蛋白表达逐渐降低。TCGA数据库分析显示，HSP90AB1低表达患者无铂治疗间隔（platinum⁃free interval, PFI）和总生存时间（overall survival,OS）显著低于高表达患者（PPFI=0.041，POS=0.013）。KEGG分析发现HSP90AB1低表达与能量代谢、细胞黏附、同源重组和铂类药物抵抗相关。稳定敲低SKOV3细胞中HSP90AB1基因的表达可增加其对顺铂的抗性（P<0.001），耐药指数为1.4。结论 HSP90AB1低表达与卵巢癌患者不良预后相关，下调卵巢癌细胞的HSP90AB1可促进铂耐药发生，HSP90AB1可能是铂耐药的关键节点基因。

关键词: 卵巢癌, HSP90AB1, 顺铂, 耐药

Abstract: Objective To investigate the effects of heat shock protein 90 kDa alpha, class B, member 1 (HSP90AB1) on the prognosis and cisplatin resistance of ovarian cancer patients. Methods Time⁃series analysis was used to analyze the changes in mRNA, miRNA, and protein levels during cisplatin resistance development in the subcutaneous nude mice xenograft tumor model to identify the potential key resistance gene HSP90AB1.Western blot was performed to detect changes in HSP90AB1 expression in xenograft tissues. Clinical prognostic data from 210 ovarian cancer patients in the TCGA database were analysed to assess the association between HSP90AB1 expression and cisplatin resistance. RNA interference was employed to knockdown HSP90AB1 expression in SKOV3 cells. The half⁃maximal inhibitory concentration (IC50) of cisplatin was calculated using the CCK⁃8 assay, and apoptosis was measured by flow cytometry. Results A total of 14 upregulated and 32 downregulated genes and proteins were screened and exhibited targeting relationships with miRNAs. By protein⁃protein interaction (PPI) analysis, the core gene HSP90AB1 of the highest⁃scoring cluster was selected for further analysis. Western blot confirmed that the expression of HSP90AB1 gradually decreased in xenograft tumors during cisplatin resistance. TCGA data analysis showed that patients with low HSP90AB1 expression had significantly shorter platinum⁃free interval (PFI) and overall survival (OS) compared to those with high expression（PPFI=0.041, POS=0.013）. KEGG pathway analysis indicated that low HSP90AB1 expression was associated with energy metabolism, cell adhesion, homologous recombination, and platinum drug resistance. Stable knockdown of HSP90AB1 gene in SKOV3 cells increased cisplatin resistance (P<0.001), with a resistance index of 1.4. Conclusions Low HSP90AB1 expression is associated with poor prognosis in ovarian cancer patients. Down⁃regulation of HSP90AB1 promotes platinum resistance in ovarian cancer cells, HSP90AB1 may be a critical regulatory gene in cisplatin resistance.  


Key words: Ovarian cancer, HSP90AB1, Cisplatin, Resistance

中图分类号: 

  • R737.31