Santos Pedro Bargão, Patel Hitendra, Henrique Rui, Félix Ana
Department of Urology, Prof. Doutor Fernando Fonseca Hospital, Amadora 2720-276, Portugal.
Department of Urology, University Hospital North Norway, Tromsø 9019, Norway.
World J Clin Oncol. 2020 Feb 24;11(2):43-52. doi: 10.5306/wjco.v11.i2.43.
Prostate cancer (PCa) is a highly prevalent malignancy and constitutes a major cause of cancer-related morbidity and mortality. It emerges through the acquisition of genetic and epigenetic alterations. Epigenetic modifications include DNA methylation, histone modifications and microRNA deregulation. These generate heritable transformations in the expression of genes but do not change the DNA sequence. Alterations in DNA methylation (hypo and hypermethylation) are the most characterized in PCa. They lead to genomic instability and inadequate gene expression. Major and minor-specific modifications in chromatin recasting are involved in PCa, with signs suggesting a dysfunction of enzymes modified by histones. MicroRNA deregulation also contributes to the initiation of PCa, including involvement in androgen receptor signalization and apoptosis. The influence of inflammation on prostate tumor carcinogenesis is currently much better known. Recent discoveries about microbial species resident in the urinary tract suggest that these are the initiators of chronic inflammation, promoting prostate inflammatory atrophy and eventually leading to PCa. Complete characterization of the relationship between the urinary microbiome and prostatic chronic inflammation will be crucial to develop plans for the prevention of PCa. The prevalent nature of epigenetic and inflammatory alterations may provide potential biomarkers for PCa diagnosis, treatment decisions, evaluation of prognosis and posttreatment surveillance.
前列腺癌（PCa）是一种高度常见的恶性肿瘤，是癌症相关发病和死亡的主要原因。它通过获得遗传和表观遗传改变而出现。表观遗传修饰包括DNA甲基化、组蛋白修饰和微小RNA失调。这些会在基因表达中产生可遗传的变化，但不会改变DNA序列。DNA甲基化的改变（低甲基化和高甲基化）在前列腺癌中最为典型。它们会导致基因组不稳定和基因表达不足。染色质重塑中的主要和次要特异性修饰都与前列腺癌有关，有迹象表明存在组蛋白修饰酶功能障碍。微小RNA失调也有助于前列腺癌的发生，包括参与雄激素受体信号传导和细胞凋亡。目前，炎症对前列腺肿瘤致癌作用的影响已广为人知。最近关于尿路中常驻微生物种类的发现表明，这些微生物是慢性炎症的引发者，会促进前列腺炎性萎缩并最终导致前列腺癌。全面了解尿路微生物群与前列腺慢性炎症之间的关系对于制定前列腺癌预防计划至关重要。表观遗传和炎症改变的普遍性质可能为前列腺癌的诊断、治疗决策、预后评估和治疗后监测提供潜在的生物标志物。
