Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3015 Rotterdam, The Netherlands.
Division of AI in Oncology, German Cancer Research Centre DKFZ, 69120 Heidelberg, Germany.
Int J Mol Sci. 2023 Mar 22;24(6):6009. doi: 10.3390/ijms24066009.
Treatment-induced AR alterations, including AR alternative splice variants (AR-Vs), have been extensively linked to harboring roles in primary and acquired resistance to conventional and next-generation hormonal therapies in prostate cancer and therefore have gained momentum. Our aim was to uniformly determine recurrent AR-Vs in metastatic castration-resistant prostate cancer (mCRPC) using whole transcriptome sequencing in order to assess which AR-Vs might hold potential diagnostic or prognostic relevance in future research. This study reports that in addition to the promising AR-V7 as a biomarker, AR45 and AR-V3 were also seen as recurrent AR-Vs and that the presence of any AR-V could be associated with higher AR expression. With future research, these AR-Vs may therefore harbor similar or complementary roles to AR-V7 as predictive and prognostic biomarkers in mCRPC or as proxies for abundant AR expression.
治疗诱导的 AR 改变，包括 AR 选择性剪接变体 (AR-Vs)，已被广泛认为在前列腺癌中对传统和下一代激素治疗的原发性和获得性耐药中起作用，因此受到了关注。我们的目的是使用全转录组测序在转移性去势抵抗性前列腺癌 (mCRPC) 中统一确定复发性 AR-Vs，以评估哪些 AR-Vs 在未来的研究中可能具有潜在的诊断或预后相关性。这项研究表明，除了有前途的 AR-V7 作为生物标志物外，AR45 和 AR-V3 也被视为复发性 AR-Vs，并且任何 AR-V 的存在都可能与更高的 AR 表达相关。随着未来的研究，这些 AR-Vs 可能与 AR-V7 具有相似或互补的作用，作为 mCRPC 的预测和预后生物标志物，或作为 AR 表达丰富的替代物。
