Barletta Francesco, Bandini Marco, Cirulli Giuseppe Ottone, Zaurito Paolo, Lucianò Roberta, Giannese Francesca, Scotti Giulia Maria, Oneto Caterina, Tenace Nazario, Scarfò Federico, Morelli Marco J, Lazarevic Dejan, De Cobelli Francesco, Ponzoni Maurilio, Doglioni Claudio, Tonon Giovanni, Gandaglia Giorgio, Montorsi Francesco, Briganti Alberto
Unit of Urology/Division of Oncology, Gianfranco Soldera Prostate Cancer Lab, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Vita-Salute San Raffaele University, Milan, Italy.
Transl Androl Urol. 2025 Feb 28;14(2):454-462. doi: 10.21037/tau-24-382. Epub 2025 Feb 25.
Epigenetics, particularly DNA methylation, plays a crucial role in gene activation and deactivation. Indeed, modification of this pathway has been well described as promoter of cancer development in many settings. Hypermethylation of CpG islands has also been described as a significant epigenetic alteration in prostate cancer (PCa), being associated with gene silencing and tumour progression. Key studies have shown that specific genes, such as , , and , exhibit significant epigenetic alterations in PCa, with their methylation profiles showing potential utility as biomarkers in the diagnostic setting. Furthermore, comprehensive methylation analyses have identified numerous differentially methylated CpGs and relative molecular pathways associated with PCa carcinogenesis and progression, thus enhancing the understanding of its molecular underpinnings. Finally, therapies targeting DNA methylation, such as DNA methyltransferases (DNMTs) inhibitors, show potential in overcoming drug resistance in advanced PCa treatment. Consequently, dissecting epigenetic mechanisms, and in particular DNA methylation, is fundamental for understanding PCa carcinogenesis, providing valuable insights for clinical decisions and development of targeted therapies. Given the above premises, this review aims to provide an overview of the role of DNA methylation aberrations in PCa, highlighting current and future directions for exploring the epigenetic landscape to better understand the origins and progression of this disease.
表观遗传学,尤其是DNA甲基化,在基因激活和失活中起着关键作用。事实上,在许多情况下,这一途径的改变已被充分描述为癌症发展的促进因素。CpG岛的高甲基化也被描述为前列腺癌(PCa)中一种重要的表观遗传改变,与基因沉默和肿瘤进展相关。关键研究表明,特定基因,如[此处原文缺失具体基因名称]、[此处原文缺失具体基因名称]和[此处原文缺失具体基因名称],在PCa中表现出显著的表观遗传改变,其甲基化谱在诊断环境中显示出作为生物标志物的潜在用途。此外,全面的甲基化分析已经确定了许多与PCa致癌作用和进展相关的差异甲基化CpG和相关分子途径,从而加深了对其分子基础的理解。最后,针对DNA甲基化的疗法,如DNA甲基转移酶(DNMTs)抑制剂,在克服晚期PCa治疗中的耐药性方面显示出潜力。因此,剖析表观遗传机制,特别是DNA甲基化,对于理解PCa致癌作用至关重要,为临床决策和靶向治疗的开发提供了有价值的见解。基于上述前提,本综述旨在概述DNA甲基化异常在PCa中的作用,强调探索表观遗传格局以更好地理解该疾病起源和进展的当前及未来方向。