An epigenetic marker panel for detection of lung cancer using cell-free serum DNA.
An epigenetic marker panel for detection of lung cancer using cell-free serum DNA.
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DOI：
10.1158/1078-0432.ccr-10-3436
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发表时间：
2011-07-01
期刊：
影响因子：
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通讯作者：
Sidransky D
中科院分区：
文献类型：
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作者：
Begum S;Brait M;Dasgupta S;Ostrow KL;Zahurak M;Carvalho AL;Califano JA;Goodman SN;Westra WH;Hoque MO;Sidransky D
我们研究了检测肺癌患者血清中一些新的和已知基因的异常DNA甲基化的可行性。为了确定分析灵敏度，我们通过使用定量甲基化特异性PCR检测了来自10名原发性肺肿瘤患者的肿瘤和匹配的血清DNA中15个基因启动子的异常甲基化。然后，我们测试了这15个基因集，以确定有限数量的肺癌患者和对照血清中更有用的DNA甲基化变化。在一个独立的集合中，我们测试了六个最有希望的基因（APC，CDH1，MGMT，DCC，RASSF1A和AIM），以进一步阐明这组标记物的诊断应用。在所有10个肺原发性肿瘤中检测到至少一个所研究基因的启动子超甲基化。在大多数情况下，血清DNA中的异常甲基化伴随着匹配的肿瘤样品中的甲基化。在独立组中，使用具有100%特异性（DCC）的单个基因，76名肺癌患者中的35.5%（95%CI 25%，47%）被正确鉴定。对于没有甲基化DCC的患者，添加基于其余5个基因的逻辑回归评分将灵敏度从35.5%提高到75%（95%CI：64%，84%），但将特异性从100%降低到73%（95%CI：54%，88%）。这种方法需要在更大的测试集中进行评估，以确定该基因集在肺癌早期检测和监测中的作用。
We investigated the feasibility of detecting aberrant DNA methylation of some novel and known genes in the serum of lung cancer patients. To determine the analytical sensitivity, we examined the tumor and the matched serum DNA for aberrant methylation of fifteen gene promoters from 10 patients with primary lung tumors by using Quantitative methylation specific PCR. We then tested this 15 gene set to identify the more useful DNA methylation changes in the serum of a limited number of lung cancer patients and controls. In an independent set, we tested the six most promising genes (APC, CDH1, MGMT, DCC, RASSF1A and AIM) for further elucidation of the diagnostic application of this panel of markers. Promoter hypermethylation of at least one of the genes studied was detected in all 10 lung primary tumors. In majority of cases, aberrant methylation in serum DNA was accompanied by methylation in the matched tumor samples. In the independent set, using a single gene that had 100% specificity (DCC), 35.5% (95% CI 25%, 47%) of the 76 lung cancer patients were correctly identified. For patients without methylated DCC, addition of a logistic regression score that was based on the five remaining genes improved sensitivity from 35.5% to 75% (95% CI: 64%, 84%) but decreased the specificity from 100% to 73% (95% CI:54%, 88%). This approach needs to be evaluated in a larger test set to determine the role of this gene set in early detection and surveillance of lung cancer.