摘要目的:探讨可变剪接事件及剪接因子对雄激素剥夺疗法（ADT）治疗的前列腺癌患者预后的预测作用。方法:从TCGA数据库下载60例进行ADT治疗的前列腺癌患者相关临床、转录组信息，并获得可变剪接事件信息。通过R语言程序包，使用LASSO、Cox回归模型筛选相关可变剪接事件及剪接因子，建立相关模型，进行独立预后分析及相关调控网络分析。结果:确定前列腺癌患者相关可变剪接事件44 070个，包含可变受体位点（AA）3 525个、可变供体位点（AD）3 101个、可变启动子（AP）9 035个、可变终止子（AT）8 663个、外显子跳跃（ES）16 772个、外显子互斥（ME）228个和内含子保留（RI）2 747个。通过单因素Cox比例风险回归模型确定1 349个可变剪接事件为与ADT相关的疾病进展相关剪接事件（DFS-SE），包括AA事件145个、AD事件102个、AP事件243个、AT事件189个、ES事件557个、ME事件6个和RI事件107个。多因素Cox回归分析显示，加入临床相关信息后，ME事件（ANK3|11852|ME、TCF7L2|151705|ME、UBR2|127390|ME、SLC39A14|140283|ME）可能为预测ADT抵抗的独立预后因子（ HR＝1.398，95% CI 1.156～1.689， P<0.01）。 结论:ME类可变剪接事件结合相关临床数据对预测前列腺癌患者ADT有效性具有一定意义，对探索前列腺癌患者ADT抵抗的研究具有重要作用。

abstractsObjective:To explore the predictive effect of alternative splicing events and splicing factors on the prognosis of prostate cancer patients with androgen deprivation therapy (ADT).Methods:The relevant clinical and transcriptome information of 60 prostate cancer patients with ADT were downloaded from TCGA database, and the alternative splicing events information was obtained. LASSO and Cox regression models were used to screen the relevant alternative splicing events and splice factors through R language package. The related model was established, and the independent prognostic analysis and related regulatory network analysis were performed.Results:A total of 44 070 associated alternate splicing events were identified in prostate cancer patients, including 3 525 alternate acceptor sites (AA), 3 101 alternate donor sites (AD), 9 035 alternate promoters (AP), 8 663 alternate terminators (AT), 16 772 exon skipping (ES), 228 exon mutual exclusion (ME), and 2 747 retained intron (RI). Through univariate Cox proportional hazard regression model, 1 349 alternate splicing events were identified as disease-free survival-related splicing events (DFS-SE) related to ADT, including 145 AA events, 102 AD events, 243 AP events, 189 AT events, 557 ES events, 6 ME events, and 107 RI events. Multivariate Cox regression analysis show that after adding clinical related information, ME events (ANK3|11852|ME, TCF7L2|151705|ME, UBR2|127390|ME and SLC39A14|140283|ME) may be independent prognostic factors for predicting ADT resistance ( HR = 1.398, 95% CI 1.156-1.689, P<0.01). Conclusion:The combination of ME-type alternate splicing events and related clinical data has certain significances in predicting the effectiveness of ADT in prostate cancer patients, and plays an important role in the research on the resistance of prostate cancer patients to ADT.