中国癌症防治杂志2025，Vol.17Issue(2)：188-195,8.DOI:10.3969/j.issn.1674-5671.2025.02.09
HSP90AB1在卵巢癌顺铂耐药形成过程中表达量的变化及其意义
Alterations of HSP90AB1 expression in ovarian cancer during cisplatin resistance and its clinical significance
摘要
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 resis-tance.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.关键词
卵巢癌/HSP90AB1/顺铂/耐药Key words
Ovarian cancer/HSP90AB1/Cisplatin/Resistance分类
临床医学引用本文复制引用
梁惠婷,闭诗雯,刘奔,陆婷婷,王琪,石丽君..HSP90AB1在卵巢癌顺铂耐药形成过程中表达量的变化及其意义[J].中国癌症防治杂志,2025,17(2):188-195,8.基金项目
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) （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) （GKE-ZZ202016）
