DNA methylation markers for risk of metastasis in a cohort of men with localized prostate cancer.

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-03-25 DOI:10.1080/15592294.2024.2308920
Talar S Habeshian, Kimberly L Cannavale, Jeff M Slezak, Yu-Hsiang Shu, Gary W Chien, XuFeng Chen, Feng Shi, Kimberly D Siegmund, Stephen K Van Den Eeden, Jiaoti Huang, Chun R Chao
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引用次数: 0

Abstract

Accurately identifying life-threatening prostate cancer (PCa) at time of diagnosis remains an unsolved problem. We evaluated whether DNA methylation status of selected candidate genes can predict the risk of metastasis beyond clinical risk factors in men with untreated PCa. A nested case-control study was conducted among men diagnosed with localized PCa at Kaiser Permanente California between 01/01/1997-12/31/2006 who did not receive curative treatments. Cases were those who developed metastasis within 10 years from diagnosis. Controls were selected using density sampling. Ninety-eight candidate genes were selected from functional categories of cell cycle control, metastasis/tumour suppressors, cell signalling, cell adhesion/motility/invasion, angiogenesis, and immune function, and 41 from pluripotency genes. Cancer DNA from diagnostic biopsy blocks were extracted and analysed. Associations of methylation status were assessed using CpG site level and principal components-based analysis in conditional logistic regressions. In 215 cases and 404 controls, 27 candidate genes were found to be statistically significant in at least one of the two analytical approaches. The agreement between the methods was 25.9% (7 candidate genes, including 2 pluripotency markers). The DNA methylation status of several candidate genes was significantly associated with risk of metastasis in untreated localized PCa patients. These findings may inform future risk prediction models for PCa metastasis beyond clinical characteristics.

局部前列腺癌男性队列中转移风险的 DNA 甲基化标记。
在诊断时准确识别危及生命的前列腺癌(PCa)仍是一个尚未解决的问题。我们评估了选定候选基因的 DNA 甲基化状态是否能预测未经治疗的 PCa 男性患者的转移风险,而不局限于临床风险因素。我们对 1997 年 1 月 1 日至 2006 年 12 月 31 日期间在加州凯撒医疗中心确诊为局部 PCa 且未接受治疗的男性患者进行了一项嵌套病例对照研究。病例为确诊后 10 年内发生转移者。对照组采用密度抽样法选出。从细胞周期控制、转移/肿瘤抑制因子、细胞信号、细胞粘附/流动/侵袭、血管生成和免疫功能等功能类别中筛选出 98 个候选基因,并从多能基因中筛选出 41 个候选基因。从诊断性活检块中提取癌症 DNA 并进行分析。在条件逻辑回归中使用 CpG 位点水平和基于主成分的分析评估甲基化状态的相关性。在 215 例病例和 404 例对照中,发现 27 个候选基因在两种分析方法中至少有一种具有统计学意义。两种方法的一致性为 25.9%(7 个候选基因,包括 2 个多能性标记)。几个候选基因的DNA甲基化状态与未经治疗的局部PCa患者的转移风险有显著相关性。除临床特征外,这些发现还可为未来的PCa转移风险预测模型提供参考。
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来源期刊
Epigenetics
Epigenetics 生物-生化与分子生物学
CiteScore
6.80
自引率
2.70%
发文量
82
审稿时长
3-8 weeks
期刊介绍: Epigenetics publishes peer-reviewed original research and review articles that provide an unprecedented forum where epigenetic mechanisms and their role in diverse biological processes can be revealed, shared, and discussed. Epigenetics research studies heritable changes in gene expression caused by mechanisms others than the modification of the DNA sequence. Epigenetics therefore plays critical roles in a variety of biological systems, diseases, and disciplines. Topics of interest include (but are not limited to): DNA methylation Nucleosome positioning and modification Gene silencing Imprinting Nuclear reprogramming Chromatin remodeling Non-coding RNA Non-histone chromosomal elements Dosage compensation Nuclear organization Epigenetic therapy and diagnostics Nutrition and environmental epigenetics Cancer epigenetics Neuroepigenetics
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