背景：许多研究已经证实了人类衰老与恶性肿瘤（特别是前列腺癌）进展之间的关联。然而，据我们所知，还没有研究全面阐明前列腺癌中衰老微环境（AME）的复杂特征。方法：采用NMF算法确定AME的调控模式。然后构建了一种衰老微环境指数（AMI），具有出色的预后和免疫疗法预测能力，并通过空间转录组学进行了临床相关性调查。此外，使用癌症药物敏感性基因组学（GDSC）、连通性图（CMap）和CellMiner数据库分析了前列腺癌患者的药物反应。最后，采用体外和体内实验研究了AME。结果：在813名前列腺癌患者中确定了三种不同的AME调控模式，与不同的临床预后和生理途径相关。基于AMI，前列腺癌患者被分为高分和低分亚组。较高的AMI分数与更多的免疫细胞浸润、生化复发率（BCR）更高以及前列腺癌对免疫疗法、抗雄激素治疗和化疗的反应更差显著相关。此外，我们发现比卡鲁胺和恶椴酚的组合能够抑制前列腺癌的肿瘤生长。此外，作为AMI的主要成分，COL1A1和BGLAP充当了癌基因的角色，并通过体内和体外实验进行了验证。结论：AME调控与TME的多样性和复杂性显著相关。对AME调控模式的定量评估可能为前列腺癌的个体化治疗提供有希望的新型分子标志物。©作者。

Background: Numerous studies have substantiated the association between aging and the progression of malignant tumors in humans, notably prostate cancer (PCa). Nevertheless, to the best of our knowledge, no studies have comprehensively elucidated the intricate characteristics of the aging microenvironment (AME) in PCa. Methods: AME regulatory patterns were determined using the NMF algorithm. Then an ageing microenvironment index (AMI) was constructed, with excellent prognostic and immunotherapy prediction ability, and its' clinical relevance was surveyed through spatial transcriptomics. Further, the drug response was analysed using the Genomics of Drug Sensitivity in Cancer (GDSC), the Connectivity Map (CMap) and CellMiner database for patients with PCa. Finally, the AME was studied using in vitro and vivo experiments. Results: Three different AME regulatory patterns were identified across 813 PCa patients, associated with distinct clinical prognosis and physiological pathways. Based on the AMI, patients with PCa were divided into the high-score and low-score subsets. Higher AMI score was significantly infiltrated with more immune cells, higher rate of biochemical recurrence (BCR) and worse response to immunotherapy, antiandrogen therapy and chemotherapy in PCa. In addition, we found that the combination of bicalutamide and embelin was capable of suppressing tumor growth of PCa. Besides, as the main components of AMI, COL1A1 and BGLAP act as oncogenes and were verified via in vivo and in vitro experiments. Conclusions: AME regulation is significantly associated with the diversity and complexity of TME. Quantitative evaluation of the AME regulatory patterns may provide promising novel molecular markers for individualised therapy in PCa.© The author(s).