PDF(Pubmed)
Abstract：
Abiraterone acetate (AA) serves as a medication for managing persistent testosterone production in patients with metastatic castration-resistant prostate cancer (mCRPC). However, its efficacy varies among individuals; thus, the identification of biomarkers to predict and follow treatment response is required. In this pilot study, we explored the potential of circulating microRNAs (c-miRNAs) to stratify patients based on their responsiveness to AA. We conducted an analysis of plasma samples obtained from a cohort of 33 mCRPC patients before and after three, six, and nine months of AA treatment. Using miRNA RT-qPCR panels for candidate discovery and TaqMan RT-qPCR for validation, we identified promising miRNA signatures. Our investigation indicated that a signature based on miR-103a-3p and miR-378a-5p effectively discriminates between non-responder and responder patients, while also following the drug\'s efficacy over time. Additionally, through in silico analysis, we identified target genes and transcription factors of the two miRNAs, including PTEN and HOXB13, which are known to play roles in AA resistance in mCRPC. In summary, our study highlights two c-miRNAs as potential companion diagnostics of AA in mCRPC patients, offering novel insights for informed decision-making in the treatment of mCRPC.
摘要：
醋酸阿比特龙（AA）可作为治疗转移性去势抵抗性前列腺癌（mCRPC）患者持续睾酮产生的药物。然而,它的功效因个体而异；因此，需要识别生物标志物来预测和跟踪治疗反应.在这项试点研究中，我们探讨了循环微小RNA(c-miRNA)根据患者对AA的反应性对患者进行分层的潜力.我们对一组33例mCRPC患者在3例之前和之后的血浆样本进行了分析，六,和9个月的AA治疗。使用miRNART-qPCR面板进行候选发现，使用TaqManRT-qPCR进行验证，我们确定了有希望的miRNA特征。我们的调查表明，基于miR-103a-3p和miR-378a-5p的签名有效区分了非应答者和应答者患者。同时也随着时间的推移跟随药物的功效。此外,通过硅分析，我们鉴定了两个miRNAs的靶基因和转录因子，包括PTEN和HOXB13，已知它们在mCRPC的AA抗性中起作用。总之,我们的研究强调了两种c-miRNAs作为mCRPC患者AA的潜在伴随诊断，为mCRPC治疗中的知情决策提供新的见解。
