Differential Methylation of Cell-Free Circulating DNA Among Patients With Pancreatic Cancer Versus Chronic Pancreatitis
Differential Methylation of Cell-Free Circulating DNA Among Patients With Pancreatic Cancer Versus Chronic Pancreatitis
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DOI：
10.1002/cncr.24893
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发表时间：
2010-04-01
期刊：
影响因子：
6.2
通讯作者：
Levenson, Victor
中科院分区：
文献类型：
--
作者：
Liggett, Thomas;Melnikov, Anatoliy;Levenson, Victor
背景：虽然慢性胰腺炎患者患胰腺癌的风险增加，但由于慢性胰腺炎和胰腺癌的症状非常相似，胰腺癌的及时检测往往是困难的。此外，继发性炎症可能在胰腺癌中被发现，从而使诊断进一步复杂化。为了提高胰腺癌患者的存活率，需要一种可靠的试验来区分慢性胰腺炎和胰腺癌。在这篇文章中，作者描述了一种无细胞血浆DNA甲基化图谱，它能以90%的准确率区分CP和PANCA。方法：采用基因芯片技术对30例CP患者、30例PANCA患者和30例健康对照(N)的血浆DNA进行甲基化分析，每个样本有56个片段。统计分析采用Fisher精确检验、朴素贝叶斯算法和25轮5重交叉验证。结果：MethDet56甲基化分析技术鉴定了17个基因启动子信息(8个用于区分N和CP，14个用于区分CP和PANCA)。敏感度为81.7%，特异度为78%(P
BACKGROUND: Although patients with chronic pancreatitis (CP) have an increased risk of pancreatic cancer (PanCa), the timely detection of PanCa often is difficult, because the symptoms of CP and PanCa are very similar. Moreover, secondary inflammation may be identified in PanCa, further complicating diagnosis. To improve the survival of patients with PanCa, a reliable test to differentiate CP from PanCa is needed. In this article, the authors describe a methylation profile of cell-free plasma DNA that distinguished CP from PanCa with >90% accuracy. METHODS: Methylation in cell-free, plasma DNA was compared among 30 samples from patients with CP, 30 samples from patients with PanCa, and 30 samples from healthy controls (N) using a microarray-mediated methylation analysis of 56 fragments in each sample (MethDet56). Statistical analysis was done by using the Fisher exact test, a naive Bayes algorithm, and 25 rounds of 5-fold cross-validation. RESULTS: The MethDet56 methylation analysis technique identified 17 gene promoters as informative (8 for distinguishing N from CP and 14 for distinguishing CP from PanCa). It achieved 81.7% sensitivity and 78% specificity (P