Demidenko Rita, Daniunaite Kristina, Bakavicius Arnas, Sabaliauskaite Rasa, Skeberdyte Aiste, Petroska Donatas, Laurinavicius Arvydas, Jankevicius Feliksas, Lazutka Juozas R, Jarmalaite Sonata
Life Sciences Centre, Vilnius University, Vilnius, Lithuania.
National Cancer Institute, Vilnius, Lithuania.
Oncotarget. 2017 Jun 27;8(37):61709-61718. doi: 10.18632/oncotarget.18683. eCollection 2017 Sep 22.
Differentiation of indolent and aggressive prostate carcinoma (PCa) at the time of diagnosis is currently one of the major challenges. This study aimed at identification of prognostic biomarkers to aid in predicting biochemical recurrence (BCR) of the disease. Microarray-based gene expression profiling in tissues of 8 BCR and 8 No-BCR cases revealed expression differences of 455 genes, most of which were down-regulated in BCR cases. Eleven genes were selected for validation by real-time PCR in the first PCa cohort (N = 55), while seven of them were further validated in the second, independent, PCa cohort (N = 53). Down-regulation of (p < 0.001) and (p = 0.002) expression and up-regulated levels of (p = 0.025) were specific biomarkers of BCR in at least one of the two PCa cohorts, but only expression retained the independent prognostic value in a multivariate analysis (p < 0.001). DNA methylation analysis (114 PCa and 24 non-cancerous tissues) showed frequent methylation in PCa (p < 0.001) and was associated (p < 0.010) with the down-regulated expression in one PCa cohort. The results of our study suggest down-regulation as a potential feature of aggressive PCa.
在诊断时区分惰性和侵袭性前列腺癌(PCa)是当前主要挑战之一。本研究旨在鉴定预后生物标志物,以帮助预测该疾病的生化复发(BCR)。对8例BCR病例和8例无BCR病例的组织进行基于微阵列的基因表达谱分析,发现455个基因存在表达差异,其中大多数基因在BCR病例中表达下调。在首个前列腺癌队列(N = 55)中选择了11个基因通过实时PCR进行验证,其中7个基因在第二个独立的前列腺癌队列(N = 53)中进一步验证。在两个前列腺癌队列中的至少一个中, (p < 0.001)和 (p = 0.002)表达下调以及 (p = 0.025)水平上调是BCR的特异性生物标志物,但在多变量分析中只有 表达保留了独立的预后价值(p < 0.001)。DNA甲基化分析(114例前列腺癌组织和24例非癌组织)显示前列腺癌中 甲基化频繁(p < 0.001),并且在一个前列腺癌队列中与表达下调相关(p < 0.010)。我们的研究结果表明 下调是侵袭性前列腺癌的一个潜在特征。