Zakari Suleiman, Rotimi Solomon O, Bholah Chandra Tatsha, Ogunlana Olubanke O
Department of Biochemistry, College of Science and Technology, Covenant University, Ota, Ogun, Nigeria.
Cancer Genomics Laboratory, Covenant Applied Informatics and Communication-Africa Centre of Excellence (CApIC-ACE), Ota, Ogun, Nigeria.
Scientifica (Cairo). 2025 May 20;2025:4084224. doi: 10.1155/sci5/4084224. eCollection 2025.
Speckle-type pox virus and zinc finger protein (SPOP) has emerged as a key focus in prostate cancer research due to its critical role in regulating the androgen receptor (AR) signaling pathway. This review aims to comprehensively summarize current knowledge on SPOP gene mutations in prostate cancer, emphasizing their importance in disease characterization and identification of therapeutic targets. A systematic literature search was conducted across multiple databases, including PubMed, Web of Science, Scopus, and Google Scholar. In addition, this study uses computational approaches and data from the TCGA cBioPortal database to explore the landscape of SPOP mutations in prostate cancer. After screening 682 articles and following systematic selection steps, 56 high-quality articles were included. Computational analysis of TCGA cBioPortal data revealed a SPOP mutation prevalence of 5%-6%, along with significant alterations in AR signaling and epigenetic regulation. SPOP mutations disrupt substrate recognition, leading to dysregulation of downstream pathways such as AR signaling and chromatin remodeling. Notably, SPOP-mutant prostate cancers are mutually exclusive with TMPRSS2-ERG fusions and enriched for Wnt pathway alterations. Patients with SPOP mutations demonstrate prolonged responses to androgen deprivation therapy (ADT), although concurrent mutations in TP53 or DNA repair genes negatively impact outcomes. While their prognostic significance continues to evolve, their impact on the AR pathway highlights their potential as therapeutic targets. The clinical implications of SPOP mutations are substantial, as they are linked to variations in treatment response and disease progression, thus serving as valuable biomarkers for risk stratification and prognosis.
斑点型痘病毒和锌指蛋白（SPOP）已成为前列腺癌研究的关键焦点，因为它在调节雄激素受体（AR）信号通路中起着至关重要的作用。本综述旨在全面总结目前关于前列腺癌中SPOP基因突变的知识，强调其在疾病特征描述和治疗靶点识别中的重要性。我们在多个数据库中进行了系统的文献检索，包括PubMed、Web of Science、Scopus和谷歌学术。此外，本研究使用计算方法和来自TCGA cBioPortal数据库的数据来探索前列腺癌中SPOP突变的情况。在筛选了682篇文章并遵循系统的选择步骤后，纳入了56篇高质量文章。对TCGA cBioPortal数据的计算分析显示，SPOP突变率为5%-6%，同时AR信号和表观遗传调控也有显著改变。SPOP突变会破坏底物识别，导致AR信号和染色质重塑等下游通路失调。值得注意的是，SPOP突变型前列腺癌与TMPRSS2-ERG融合相互排斥，且Wnt通路改变更为丰富。携带SPOP突变的患者对雄激素剥夺治疗（ADT）有较长的反应，尽管TP53或DNA修复基因的并发突变会对结果产生负面影响。虽然它们的预后意义仍在不断演变，但它们对AR通路的影响凸显了其作为治疗靶点的潜力。SPOP突变的临床意义重大，因为它们与治疗反应和疾病进展的差异有关，因此可作为风险分层和预后的有价值生物标志物。
