Viet Chi T, Schmidt Brian L
Department of Oral and Maxillofacial Surgery, C-522, University of California, San Francisco, San Francisco, CA 94143-0440, USA.
Cancer Epidemiol Biomarkers Prev. 2008 Dec;17(12):3603-11. doi: 10.1158/1055-9965.EPI-08-0507.
To perform methylation array analysis of 807 cancer-associated genes using tissue and saliva of oral squamous cell carcinoma (OSCC) patients with the objective of identifying highly methylated gene loci that hold diagnostic and predictive value as a biomarker.
We did the methylation array on DNA extracted from preoperative saliva, postoperative saliva, and tissue of 13 patients with OSCC, and saliva of 10 normal subjects. We identified sites that were highly methylated in the tissue and preoperative saliva samples but not methylated in the postoperative saliva samples or in normal subjects.
High quality DNA was obtained and the methylation array was successfully run on all samples. We identified significant differences in methylation patterns between the preoperative and postoperative saliva from cancer patients. We established a gene classifier consisting of 41 gene loci from 34 genes that showed methylation in preoperative saliva and tissue but were not methylated in postoperative saliva or normal subjects. Gene panels of 4 to 10 genes were constructed from genes in the classifier. The panels had a sensitivity of 62% to 77% and a specificity of 83% to 100% for OSCC.
We report methylation array analysis of 807 cancer-associated genes in the saliva of oral cancer patients before and after oral cancer resection. Our methylation biomarker approach shows the proof of principle that methylation array analysis of saliva can produce a set of cancer-related genes that are specific and can be used as a composite biomarker for the early detection of oral cancer.
利用口腔鳞状细胞癌（OSCC）患者的组织和唾液对807个癌症相关基因进行甲基化阵列分析，以鉴定具有诊断和预测价值的高甲基化基因位点作为生物标志物。
我们对13例OSCC患者的术前唾液、术后唾液和组织以及10例正常受试者的唾液提取的DNA进行甲基化阵列分析。我们鉴定出在组织和术前唾液样本中高度甲基化但在术后唾液样本或正常受试者中未甲基化的位点。
获得了高质量的DNA，并且在所有样本上成功进行了甲基化阵列分析。我们发现癌症患者术前和术后唾液的甲基化模式存在显著差异。我们建立了一个基因分类器，由34个基因的41个基因位点组成，这些基因位点在术前唾液和组织中显示甲基化，但在术后唾液或正常受试者中未甲基化。从分类器中的基因构建了4至10个基因的基因面板。这些面板对OSCC的敏感性为62%至77%，特异性为83%至100%。
我们报告了口腔癌切除前后口腔癌患者唾液中807个癌症相关基因的甲基化阵列分析。我们的甲基化生物标志物方法证明了这样一个原理，即唾液的甲基化阵列分析可以产生一组特定的癌症相关基因，可作为早期检测口腔癌的复合生物标志物。
