PDF(Pubmed)
Abstract：
Differentially methylated CpG sites (dmCpGs) that distinguish prostate tumour from adjacent benign tissue could aid in the diagnosis and prognosis of prostate cancer. Previously, the identification of such dmCpGs has only been undertaken in radical prostatectomy (RP) samples and not primary diagnostic tumour samples (needle biopsy or transurethral resection of the prostate). We interrogated an Australian dataset comprising 125 tumour and 43 adjacent histologically benign diagnostic tissue samples, including 41 paired samples, using the Infinium Human Methylation450 BeadChip. Regression analyses of paired tumour and adjacent benign samples identified 2,386 significant dmCpGs (Bonferroni p < 0.01; delta-β ≥ 40%), with LASSO regression selecting 16 dmCpGs that distinguished tumour samples in the full Australian diagnostic dataset (AUC = 0.99). Results were validated in independent North American (npaired = 19; AUC = 0.87) and The Cancer Genome Atlas (TCGA; npaired = 50; AUC = 0.94) RP datasets. Two of the 16 dmCpGs were in genes that were significantly down-regulated in Australian tumour samples (Bonferroni p < 0.01; GSTM2 and PRKCB). Ten additional dmCpGs distinguished low (n = 34) and high Gleason (n = 88) score tumours in the diagnostic Australian dataset (AUC = 0.95), but these performed poorly when applied to the RP datasets (North American: AUC = 0.66; TCGA: AUC = 0.62). The DNA methylation marks identified here could augment and improve current diagnostic tests and/or form the basis of future prognostic tests.
摘要：
区分前列腺肿瘤与邻近良性组织的差异甲基化CpG位点（dmCpG）可以帮助前列腺癌的诊断和预后。以前,此类dmCpG的鉴定仅在根治性前列腺切除术（RP）样本中进行，而不是在原发性诊断肿瘤样本（穿刺活检或经尿道前列腺切除术）中进行。我们查询了澳大利亚的数据集，该数据集包含125个肿瘤和43个相邻的组织学良性诊断组织样本，包括41个配对的样本,使用InfiniumHumanMethylation450BeadChip。配对肿瘤和邻近良性样本的回归分析确定了2,386个显著的dmCpG（Bonferronip<0.01；δ-β≥40％），LASSO回归选择16个dmCpG，可在完整的澳大利亚诊断数据集中区分肿瘤样本（AUC=0.99）。结果在独立的北美（n配对=19;AUC=0.87）和癌症基因组图谱（TCGA;n配对=50;AUC=0.94）RP数据集中进行了验证。16个dmCpG中有两个在澳大利亚肿瘤样品中显著下调的基因中(Bonferronip<0.01;GSTM2和PRKCB)。10个额外的dmCpG区分低（n=34）和高格里森（n=88）评分的肿瘤诊断澳大利亚数据集（AUC=0.95），但应用于RP数据集时表现不佳(北美:AUC=0.66;TCGA:AUC=0.62)。此处鉴定的DNA甲基化标记可以增强和改善当前的诊断测试和/或形成未来预后测试的基础。
