一种综合的多组学分析方法，用于鉴定与前列腺癌风险相关的候选 DNA 甲基化生物标志物。
An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk.
机构信息
Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA.
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
出版信息
Nat Commun. 2020 Aug 6;11(1):3905. doi: 10.1038/s41467-020-17673-9.
It remains elusive whether some of the associations identified in genome-wide association studies of prostate cancer (PrCa) may be due to regulatory effects of genetic variants on CpG sites, which may further influence expression of PrCa target genes. To search for CpG sites associated with PrCa risk, here we establish genetic models to predict methylation (N = 1,595) and conduct association analyses with PrCa risk (79,194 cases and 61,112 controls). We identify 759 CpG sites showing an association, including 15 located at novel loci. Among those 759 CpG sites, methylation of 42 is associated with expression of 28 adjacent genes. Among 22 genes, 18 show an association with PrCa risk. Overall, 25 CpG sites show consistent association directions for the methylation-gene expression-PrCa pathway. We identify DNA methylation biomarkers associated with PrCa, and our findings suggest that specific CpG sites may influence PrCa via regulating expression of candidate PrCa target genes.
前列腺癌（PrCa）全基因组关联研究中确定的一些关联是否可能是由于遗传变异对 CpG 位点的调控作用所致，而这些作用可能进一步影响 PrCa 靶基因的表达，这一点仍然难以捉摸。为了寻找与 PrCa 风险相关的 CpG 位点，我们在这里建立了遗传模型来预测甲基化（N=1595），并进行了与 PrCa 风险的关联分析（79194 例病例和 61112 例对照）。我们确定了 759 个与前列腺癌风险相关的 CpG 位点，其中包括 15 个位于新的位点。在这 759 个 CpG 位点中，有 42 个的甲基化与 28 个相邻基因的表达相关。在这 22 个基因中，有 18 个与 PrCa 风险相关。总的来说，25 个 CpG 位点在甲基化-基因表达-PrCa 通路中表现出一致的关联方向。我们确定了与 PrCa 相关的 DNA 甲基化生物标志物，我们的研究结果表明，特定的 CpG 位点可能通过调节候选 PrCa 靶基因的表达来影响 PrCa。
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