International Journal of Oncology, 2017, 51(1):223-234.
Effects of genistein supplementation on genome‑wide DNA methylation and gene expression in patients with localized prostate cancer
Birdal Bilir, Nitya V Sharma, Jeongseok Lee, et al
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA; et al
Epidemiological studies have shown that dietary compounds have significant effects on prostate carcinogenesis. Among dietary agents, genistein, the major isoflavone in soybean, is of particular interest because high consumption of soy products has been associated with a low incidence of prostate cancer, suggesting a preventive role of genistein in prostate cancer. In spite of numerous studies to understand the effects of genistein on prostate cancer, the mechanisms of action have not been fully elucidated. We investigated the differences in methylation and gene expression levels of prostate specimens from a clinical trial of genistein supplementation prior to prostatectomy using Illumina HumanMethylation450 and Illumina HumanHT-12 v4 Expression BeadChip Microarrays. The present study was a randomized, placebo-controlled, double-blind clinical trial on Norwegian patients who received 30 mg genistein or placebo capsules daily for 3-6 weeks before prostatectomy. Gene expression changes were validated by quantitative PCR (qPCR). Whole genome methylation and expression profiling identified differentially methylated sites and expressed genes between placebo and genistein groups. Differentially regulated genes were involved in developmental processes, stem cell markers, proliferation and transcriptional regulation. Enrichment analysis suggested overall reduction in MYC activity and increased PTEN activity in genistein-treated patients. These findings highlight the effects of genistein on global changes in gene expression in prostate cancer and its effects on molecular pathways involved in prostate tumorigenesis.
希腊《国际肿瘤学杂志》，2017年
金雀异黄素补充剂对局部前列腺癌患者的全基因组DNA甲基化和基因表达的影响
伯导 比利尔，尼提亚 V 莎尔玛，等
美国亚特兰大埃默里大学病理与实验医学系，等
流行病学研究表明饮食化合物对前列腺癌发生有显着影响。在饮食中，染料木素，主要的异黄酮大豆是特别感兴趣的，因为高消费大豆产品与前列腺癌的发病率较低有关，提示染料木素在前列腺中的预防作用癌症。尽管有大量的研究了解效果的染料木素对前列腺癌的作用机制有尚未完全阐明。我们调查了差异前列腺标本的甲基化和基因表达水平来自染料木素补充的临床试验前列腺切除术使用Illumina HumanMethylation450和Illumina HumanHT-12 v4表达eadChip微阵列。本研究是一项随机，安慰剂对照，挪威患者接受双盲临床试验每天服用30毫克染料木素或安慰剂胶囊3-6周前列腺切除术。基因表达变化经过验证定量PCR（qPCR）。全基因组甲基化和表达谱分析鉴定出差异甲基化位点并在安慰剂和染料木素组之间表达基因。差异调控基因参与发育过程，干细胞标记，增殖和转录规。丰富分析表明总体减少MYC活性和染料木黄酮治疗的PTEN活性升高耐心。这些发现突出了染料木素的作用前列腺癌基因表达的全球变化及其对参与前列腺肿瘤发生的分子途径的影响。
