Department of Cancer Prevention, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.
Mol Cancer. 2011 Jul 21;10:85. doi: 10.1186/1476-4598-10-85.
The presence of cancer-specific DNA methylation patterns in epithelial colorectal cells in human feces provides the prospect of a simple, non-invasive screening test for colorectal cancer and its precursor, the adenoma. This study investigates a panel of epigenetic markers for the detection of colorectal cancer and adenomas.
Candidate biomarkers were subjected to quantitative methylation analysis in test sets of tissue samples from colorectal cancers, adenomas, and normal colonic mucosa. All findings were verified in independent clinical validation series. A total of 523 human samples were included in the study. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the biomarker panel.
Promoter hypermethylation of the genes CNRIP1, FBN1, INA, MAL, SNCA, and SPG20 was frequent in both colorectal cancers (65-94%) and adenomas (35-91%), whereas normal mucosa samples were rarely (0-5%) methylated. The combined sensitivity of at least two positives among the six markers was 94% for colorectal cancers and 93% for adenoma samples, with a specificity of 98%. The resulting areas under the ROC curve were 0.984 for cancers and 0.968 for adenomas versus normal mucosa.
The novel epigenetic marker panel shows very high sensitivity and specificity for both colorectal cancers and adenomas. Our findings suggest this biomarker panel to be highly suitable for early tumor detection.
人类粪便中上皮性结直肠细胞中存在癌症特异性 DNA 甲基化模式，为结直肠癌及其前体腺瘤提供了一种简单、非侵入性的筛查检测方法。本研究调查了一组用于检测结直肠癌和腺瘤的表观遗传标记物。
在结直肠癌、腺瘤和正常结肠黏膜的组织样本测试集中，对候选生物标志物进行定量甲基化分析。所有发现均在独立的临床验证系列中得到验证。共有 523 个人类样本纳入研究。使用受试者工作特征 (ROC) 曲线分析来评估生物标志物组合的性能。
基因 CNRIP1、FBN1、INA、MAL、SNCA 和 SPG20 的启动子过度甲基化在结直肠癌 (65-94%) 和腺瘤 (35-91%) 中均很常见，而正常黏膜样本很少发生甲基化 (0-5%)。六个标记物中至少有两个阳性的组合对结直肠癌的敏感性为 94%，对腺瘤样本的敏感性为 93%，特异性为 98%。ROC 曲线下的面积分别为癌症的 0.984 和腺瘤的 0.968 与正常黏膜相比。
新型表观遗传标记物组合对结直肠癌和腺瘤具有非常高的敏感性和特异性。我们的研究结果表明，该生物标志物组合非常适合早期肿瘤检测。
