Li Haopeng, Wang Xin'an, Zhai Menghe, Xu Chengdang, Chen Xi
Department of Urology, Tongji Hospital, School of Medicine, Tongji University, 389 Xincun Road, Shanghai, 200065, China.
Department of Urology, Jiaxing Second Hospital, 397 North Huancheng Road, Jiaxing, 314000, Zhejiang, China.
Discov Oncol. 2024 May 10;15(1):152. doi: 10.1007/s12672-024-00973-7.
Castration-resistant prostate cancer (CRPC) represents the final stage of prostate cancer (PCa). Cabazitaxel, a taxane chemotherapy drug, is used in treating CRPC. However, patients with CRPC eventually develop resistance to cabazitaxel, and the underlying mechanism remains unclear. Here, we aimed to investigate potential genetic alterations that may play a role in CRPC resistance to cabazitaxel. Using microarray data from the GSE158494 dataset, we identified ten critical genes (CXCL8, ITGB8, CLIP4, MAP1B, WIPI1, MMP13, CXCL1, C1S, GOLGA8B, and CXCL6) associated with CRPC cell resistance to cabazitaxel. The potential function of these key genes in PCa progression was analyzed using different databases, including Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Chinese Prostate Cancer Genome and Epigenome Atlas (CPGEA). Our findings revealed altered expression of these genes in the development of PCa. Furthermore, CXCL1 and GOLGA8B were found to influence the disease-free survival (DFS) status of patients with PCa, with GOLGA8B affecting the overall prognosis in patients with PCa. Additionally, GOLGA8B expression was associated with the infiltration of various immune cells in PCa, and it was upregulated in clinical PCa and CRPC samples. Through CCK-8 assays, we established that GOLGA8B could influence the sensitivity of CRPC cells to cabazitaxel and docetaxel. In conclusion, we identified GOLGA8B as a crucial gene that influences PCa progression and contributes to CRPC resistance to cabazitaxel.
去势抵抗性前列腺癌(CRPC)是前列腺癌(PCa)的终末期。卡巴他赛是一种紫杉烷类化疗药物,用于治疗CRPC。然而,CRPC患者最终会对卡巴他赛产生耐药性,其潜在机制尚不清楚。在此,我们旨在研究可能在CRPC对卡巴他赛耐药中起作用的潜在基因改变。利用GSE158494数据集的微阵列数据,我们鉴定出与CRPC细胞对卡巴他赛耐药相关的10个关键基因(CXCL8、ITGB8、CLIP4、MAP1B、WIPI1、MMP13、CXCL1、C1S、GOLGA8B和CXCL6)。使用不同的数据库,包括基因表达综合数据库(GEO)、癌症基因组图谱(TCGA)和中国前列腺癌基因组与表观基因组图谱(CPGEA),分析了这些关键基因在PCa进展中的潜在功能。我们的研究结果揭示了这些基因在PCa发展过程中的表达变化。此外,发现CXCL1和GOLGA8B会影响PCa患者的无病生存期(DFS)状态,其中GOLGA8B影响PCa患者的总体预后。此外,GOLGA8B的表达与PCa中各种免疫细胞的浸润相关,并且在临床PCa和CRPC样本中上调。通过CCK-8实验,我们证实GOLGA8B可影响CRPC细胞对卡巴他赛和多西他赛的敏感性。总之,我们鉴定出GOLGA8B是一个影响PCa进展并导致CRPC对卡巴他赛耐药的关键基因。