Melnikov Anatoliy, Scholtens Denise, Godwin Andrew, Levenson Victor
Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
J Mol Diagn. 2009 Jan;11(1):60-65. doi: 10.2353/jmoldx.2009.080072. Epub 2008 Dec 12.
An accurate biomarker for detection of ovarian cancer may reduce cancer-related mortality. Using a previously developed microarray-based technique, we evaluated differences in DNA methylation profiles in a panel of 56 genes using sections of serous papillary adenocarcinomas and uninvolved ovaries (n=30) from women in a high-risk group. Methylation profiles were also generated for circulating DNA from blood of patients (n=33) and healthy controls (n=33). Using the most differentially methylated genes for naïve Bayesian analysis, we identified ten of these profiles as potentially informative in tissues. Various combinations of these genes produced 69% sensitivity and 70% specificity for cancer detection as estimated under a stratified, fivefold cross-validation protocol. In plasma, five genes were identified as informative; their combination had 85% sensitivity and 61% specificity for cancer detection. These results suggest that differential methylation profiling in heterogeneous samples has the potential to identify components of a composite biomarker that may detect ovarian cancer in blood with significant accuracy.
一种用于检测卵巢癌的准确生物标志物可能会降低癌症相关死亡率。我们使用先前开发的基于微阵列的技术,利用高危组女性的浆液性乳头状腺癌切片和未受累卵巢组织(n = 30),评估了56个基因的DNA甲基化谱差异。还对患者血液(n = 33)和健康对照者血液(n = 33)中的循环DNA进行了甲基化谱分析。利用对朴素贝叶斯分析中甲基化差异最大的基因,我们在组织中确定了其中10种谱型可能具有信息价值。根据分层五重交叉验证方案估计,这些基因的各种组合在癌症检测中产生了69%的灵敏度和70%的特异性。在血浆中,确定了5个基因具有信息价值;它们的组合在癌症检测中具有85%的灵敏度和61%的特异性。这些结果表明,异质性样本中的差异甲基化谱分析有可能识别出复合生物标志物的组成部分,这些组成部分可能以显著的准确性检测出血液中的卵巢癌。