前列腺癌(PC)是男性中一种潜在的沉默杀手。2018年，PC造成了超过35万人死亡，同时超过120万人被诊断出患病。多西他赛是一种属于紫杉醇类药物的化疗药物，是治疗晚期前列腺癌最有效的药物之一。然而，前列腺癌细胞经常会对该疗法产生抗药性，因此需要寻找补充和替代疗法。槲皮素是一种广泛存在于植物中的生物化合物，具有许多药理特性，已报道能够逆转多西他赛抗性前列腺癌(DRPC)中的多西他赛抵抗。因此，本研究旨在探究槲皮素逆转DRPC中的DR的机制，使用综合功能网络和探索性癌症基因组数据分析。槲皮素的潜在靶点从相关数据库中检索，而多西他赛抗性前列腺癌(DRPC)的差异表达基因(DEGs)则通过分析从基因表达 omnibus (GEO)数据库中检索的微阵列数据来确定。随后，从STRING中检索了DEGs和槲皮素靶点之间的重叠基因的蛋白质相互作用 (PPI)网络，使用Cytoscape的CytoHubba插件识别代表网络关键相互作用基因的中心基因。对中心基因进行全面分析，以确定它们对前列腺癌患者的免疫微环境和总生存期(OS)的贡献，同时还揭示了它们在前列腺癌患者中的变化。中心基因在抗化疗抵抗中发挥的生物学作用包括促进发育过程、促进基因表达、抑制细胞死亡、上皮细胞分化等。进一步的分析揭示表皮生长因子受体(EGFR)是槲皮素逆转DRPC中最相关的靶点，分子对接模拟揭示了槲皮素与EGFR之间的有效相互作用。最终，本研究为进一步探索槲皮素与多西他赛的联合治疗提供了科学依据。©2023. 作者。

Prostate cancer (PC) is a silent but potent killer among men. In 2018, PC accounted for more than 350, 000 death cases while more than 1.2 million cases were diagnosed. Docetaxel, a chemotherapeutic drug belonging to the taxane family of drugs, is one of the most potent drugs in combating advanced PC. However, PC cells often evolve resistance against the regimen. Hence, necessitating the search for complementary and alternative therapies. Quercetin, a ubiquitous phytocompound with numerous pharmacological properties, has been reported to reverse docetaxel resistance (DR) in docetaxel-resistant prostate cancer (DRPC). Therefore, this study aimed to explore the mechanism via which quercetin reverses DR in DRPC using an integrative functional network and exploratory cancer genomic data analyses.The putative targets of quercetin were retrieved from relevant databases, while the differentially expressed genes (DEGs) in docetaxel-resistant prostate cancer (DRPC) were identified by analysing microarray data retrieved from the Gene Expression Omnibus (GEO) database. Subsequently, the protein-protein interaction (PPI) network of the overlapping genes between the DEGs and quercetin targets was retrieved from STRING, while the hub genes, which represent the key interacting genes of the network, were identified using the CytoHubba plug-in of Cytoscape. The hub genes were further subjected to a comprehensive analysis aimed at identifying their contribution to the immune microenvironment and overall survival (OS) of PC patients, while their alterations in PC patients were also revealed. The biological roles played by the hub genes in chemotherapeutic resistance include the positive regulation of developmental process, positive regulation of gene expression, negative regulation of cell death, and epithelial cell differentiation among others.Further analysis revealed epidermal growth factor receptor (EGFR) as the most pertinent target of quercetin in reversing DR in DRPC, while molecular docking simulation revealed an effective interaction between quercetin and EGFR. Ultimately, this study provides a scientific rationale for the further exploration of quercetin as a combinational therapy with docetaxel.© 2023. The Author(s).