去势抵抗性前列腺癌(CRPC)代表前列腺癌(PCa)的最后阶段。卡巴他赛,紫杉烷化疗药物,用于治疗CRPC。然而,CRPC患者最终对卡巴他赛产生耐药性,和潜在的机制仍不清楚。这里,我们的目的是调查可能在CRPC对卡巴他赛耐药中起作用的潜在遗传改变.使用来自GSE158494数据集的微阵列数据,我们确定了十个关键基因(CXCL8,ITGB8,CLIP4,MAP1B,WIPI1,MMP13,CXCL1,C1S,GOLGA8B,和CXCL6)与CRPC细胞对卡巴他赛的抗性相关。使用不同的数据库分析了这些关键基因在PCa进展中的潜在功能,包括基因表达综合(GEO),癌症基因组图谱(TCGA)和中国前列腺癌基因组和表观基因组图谱(CPGEA)。我们的发现揭示了这些基因在PCa发育中的表达改变。此外,CXCL1和GOLGA8B被发现影响PCa患者的无病生存(DFS)状态,GOLGA8B影响PCa患者的整体预后。此外,GOLGA8B的表达与PCa中各种免疫细胞的浸润有关,并且在临床PCa和CRPC样本中上调。通过CCK-8检测,我们确定GOLGA8B可以影响CRPC细胞对卡巴他赛和多西他赛的敏感性.总之,我们确定GOLGA8B是影响PCa进展并导致CRPC对卡巴他赛耐药的关键基因.
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.