膀胱癌（BCa）是一种高度致命的泌尿系统恶性肿瘤，其特征在于其显着的组织学异质性。自噬已迅速成为多种癌症类型的诊断和预后生物标志物。尽管如此，目前可获得的针对 BCa 的自噬相关特征仍然有限。通过 10 倍交叉验证框架开发了一种精炼的自噬相关特征，结合了 101 种机器学习算法组合。对这一特征在预测预后和免疫治疗反应方面的表现进行了彻底评估，并探索了潜在的药物靶点和化合物。通过体外和体内实验验证了hub基因的调控机制。与大多数临床特征和其他已开发的标志物相比，自噬相关预后特征（ARPS）在预测BCa预后方面表现出优越的性能。较高的 ARPS 与较差的预后和对免疫治疗的敏感性降低相关。针对高 ARPS 组患者筛选了四个潜在靶点和五种治疗药物。体外和体内实验已证实 FKBP9 促进 BCa 的增殖、侵袭和转移。总的来说，我们的研究开发了一种有价值的工具来优化 BCa 患者的风险分层和决策。版权所有 © 2024。由 Elsevier B.V. 出版。

Bladder cancer (BCa) is a highly lethal urological malignancy characterized by its notable histological heterogeneity. Autophagy has swiftly emerged as a diagnostic and prognostic biomarker in diverse cancer types. Nonetheless, the currently accessible autophagy-related signature specific to BCa remains limited.A refined autophagy-related signature was developed through a 10-fold cross-validation framework, incorporating 101 combinations of machine learning algorithms. The performance of this signature in predicting prognosis and response to immunotherapy was thoroughly evaluated, along with an exploration of potential drug targets and compounds. In vitro and in vivo experiments were conducted to verify the regulatory mechanism of hub gene.The autophagy-related prognostic signature (ARPS) has exhibited superior performance in predicting the prognosis of BCa compared to the majority of clinical features and other developed markers. Higher ARPS is associated with poorer prognosis and reduced sensitivity to immunotherapy. Four potential targets and five therapeutic agents were screened for patients in the high-ARPS group. In vitro and vivo experiments have confirmed that FKBP9 promotes the proliferation, invasion, and metastasis of BCa.Overall, our study developed a valuable tool to optimize risk stratification and decision-making for BCa patients.Copyright © 2024. Published by Elsevier B.V.