作为最常见的非上皮恶性肿瘤，前列腺腺癌（PRAD）是男性癌症死亡的第五大原因。晚期的PRAD常发生远处转移，大多数病人死于此。然而，PRAD进展和转移的机制仍然不明确。广泛报道超过94%的基因在人类中选择性剪接，许多亚型与癌症进展和转移特别相关。剪接体突变以互斥方式在乳腺癌中发生，并且剪接体的不同组分是不同类型乳腺癌的体细胞突变的靶点。现有证据强烈支持替代剪接在乳腺癌生物学中的关键作用，并且正在开发创新工具以利用剪接事件进行诊断和治疗。为了确定PRAD转移是否与替代剪接事件（ASEs）有关，从癌症基因组图谱（TCGA）和TCGASpliceSeq数据库检索了500名PRAD患者的RNA测序数据和ASEs数据。通过Lasso回归筛选了五个基因构建预测模型，通过ROC曲线表现出良好的可靠性。此外，单变量和多变量Cox回归分析结果均证实了预测模型的良好预后疗效（P <0.001）。此外，建立了潜在的剪接调节网络，并经过多个数据库验证，我们认为HSPB1上调PIP5K1C-46,721-AT（P <0.001）的信号轴可能通过阿尔茨海默病途径的关键成员（SRC、EGFR、MAPT、APP和PRKCA）（P <0.001）介导PRAD的肿瘤发生、进展和转移。©2023。作者（们）。

As the most common nonepithelial malignancy, prostate adenocarcinoma (PRAD) is the fifth chief cause of cancer mortality in men. Distant metastasis often occurs in advanced PRAD and most patients are dying from it. However, the mechanism of PRAD progression and metastasis is still unclear. It's widely reported that more than 94% of genes are selectively splicing in humans and many isoforms are particularly related with cancer progression and metastasis. Spliceosome mutations occur in a mutually exclusive manner in breast cancer, and different components of spliceosomes are targets of somatic mutations in different types of breast cancer. Existing evidence strongly supports the key role of alternative splicing in breast cancer biology, and innovative tools are being developed to use splicing events for diagnostic and therapeutic purposes. In order to identify if the PRAD metastasis is associated with alternative splicing events (ASEs), the RNA sequencing data and ASEs data of 500 PRAD patients were retrieved from The Cancer Genome Atlas (TCGA) and TCGASpliceSeq databases. By Lasso regression, five genes were screened to construct the prediction model, with a good reliability by ROC curve. Additionally, results in both univariate and multivariate Cox regression analysis confirmed the well prognosis efficacy of the prediction model (both P < 0.001). Moreover, a potential splicing regulatory network was established and after multiple-database validation, we supposed that the signaling axis of HSPB1 up-regulating the PIP5K1C - 46,721 - AT (P < 0.001) might mediate the tumorigenesis, progression and metastasis of PRAD via the key members of Alzheimer's disease pathway (SRC, EGFR, MAPT, APP and PRKCA) (P < 0.001).© 2023. The Author(s).