A Panel of Novel Detection and Prognostic Methylated DNA Markers in Primary Non-Small Cell Lung Cancer and Serum DNA
A Panel of Novel Detection and Prognostic Methylated DNA Markers in Primary Non-Small Cell Lung Cancer and Serum DNA
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DOI：
10.1158/1078-0432.ccr-17-1222
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发表时间：
2017-11-15
影响因子：
11.5
通讯作者：
Hoque, Mohammad Obaidul
中科院分区：
文献类型：
--
作者：
Ooki, Akira;Maleki, Zahra;Hoque, Mohammad Obaidul
目的：建立一组新的癌症特异性甲基化基因，用于早期非小细胞肺癌（NSCLC）的癌症检测和预后分层。用bumphunter在“The Cancer Genome Atlas（TCGA）”数据集上进行差异甲基化区域（DMR）的鉴定，并在多组原发性NSCLC和体液（包括血清，胸腔积液，结果：从TCGA数据集中选择6个基因（CDO 1、HOXA 9、AJAP 1、PTGDR、UNCX和MARCH 11）的甲基化组。在92.2%（83/90）的训练队列中检测到基因组的启动子甲基化，特异性为72.0%（18/25），在93.0%（40/43）的IA期原发性NSCLC独立队列中检测到基因组的启动子甲基化。在43例IA晚期受试者和42例人群匹配的对照受试者的血清样本中，基因组产生的敏感性为72.1%（31/41），特异性为71.4%（30/42）。在胸腔积液和腹水样本中观察到类似的诊断准确性。基于CDO 1、HOXA 9、PTGDR和AJAP 1甲基化状态的预后风险分类将结果的风险分层作为早期疾病的独立预后因素。此外，HOXA 9，主要是过表达的HOXA 9甲基化的受试者，parabolic组，表现出较差的outcomes.Conclusions：启动子甲基化的一组6个基因有可能作为一种生物标志物，用于早期癌症检测和预测预后的诊断时间。(C)2017年AACR。
Purpose: To establish a novel panel of cancer-specific methylated genes for cancer detection and prognostic stratification of early-stage non-small cell lung cancer (NSCLC).Experimental Design: Identification of differentially methylated regions (DMR) was performed with bumphunter on "The Cancer Genome Atlas (TCGA)" dataset, and clinical utility was assessed using quantitative methylation-specific PCR assay in multiple sets of primary NSCLC and body fluids that included serum, pleural effusion, and ascites samples.Results: A methylation panel of 6 genes (CDO1, HOXA9, AJAP1, PTGDR, UNCX, and MARCH11) was selected from TCGA dataset. Promoter methylation of the gene panel was detected in 92.2% (83/90) of the training cohort with a specificity of 72.0% (18/25) and in 93.0% (40/43) of an independent cohort of stage IA primary NSCLC. In serum samples from the later 43 stage IA subjects and population-matched 42 control subjects, the gene panel yielded a sensitivity of 72.1% (31/41) and specificity of 71.4% (30/42). Similar diagnostic accuracy was observed in pleural effusion and ascites samples. A prognostic risk category based on the methylation status of CDO1, HOXA9, PTGDR, and AJAP1 refined the risk stratification for outcomes as an independent prognostic factor for an early-stage disease. Moreover, the paralog group for HOXA9, predominantly overexpressed in subjects with HOXA9 methylation, showed poor outcomes.Conclusions: Promoter methylation of a panel of 6 genes has potential for use as a biomarker for early cancer detection and to predict prognosis at the time of diagnosis. (C) 2017 AACR.