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（P_PFI=0.041, P_OS=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