Geng Junfeng, Sun Jinfeng, Lin Qiang, Gu Jun, Zhao Yangxing, Zhang Hongyu, Feng Xu, He Yinghua, Wang Wei, Zhou Xiaoyu, Yu Jian
Department of General Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, P.R. China.
Oncol Lett. 2012 Apr 1;3(4):901-906. doi: 10.3892/ol.2012.587. Epub 2012 Feb 1.
In our previous study, we attempted to develop a tool for the early diagnosis of non-small cell lung cancer (NSCLC) using DNA methylation biomarkers. With the aim of improving the diagnostic potential by optimizing the composition of the target set, in this study, 13 candidate genes (ACTA1, AIDH1A2, CBX8, CDH8, EVX1, MGC16275, NEUROG1, NEUROG2, NID2, OTX2OS1, PGAM2, PHOX2B and TOX) were analyzed by methylation-specific PCR to determine the methylation status of each gene in 5 NSCLC cell lines and in lung tissue samples from 15 healthy volunteers, 103 stage I NSCLC patients and 26 non-cancerous control patients. Results showed that NEUROG2 and NID2 were hypermethylated in stage I NSCLC tissues (31.07 and 46.60%, respectively) and unmethylated in normal lung tissues (0/15) and non-cancerous tissues (0/26). Following recombination, an optimized 5-gene panel (NEUROG2, NID2, RASSF1A, APC and HOXC9) achieved a sensitivity of 91.26% with a specificity of 84.62% in the detection of stage I NSCLC. The optimized 5-gene panel greatly improved the diagnostic power for stage I NSCLC.
在我们之前的研究中,我们尝试开发一种利用DNA甲基化生物标志物进行非小细胞肺癌(NSCLC)早期诊断的工具。为了通过优化目标集的组成来提高诊断潜力,在本研究中,通过甲基化特异性PCR分析了13个候选基因(ACTA1、AIDH1A2、CBX8、CDH8、EVX1、MGC16275、NEUROG1、NEUROG2、NID2、OTX2OS1、PGAM2、PHOX2B和TOX),以确定5种NSCLC细胞系以及来自15名健康志愿者、103名I期NSCLC患者和26名非癌对照患者的肺组织样本中每个基因的甲基化状态。结果显示,NEUROG2和NID2在I期NSCLC组织中呈高甲基化(分别为31.07%和46.60%),而在正常肺组织(15例中0例)和非癌组织(26例中0例)中呈未甲基化状态。重组后,优化的5基因组合(NEUROG2、NID2、RASSF1A、APC和HOXC9)在检测I期NSCLC时灵敏度达到91.26%,特异性为84.62%。优化的5基因组合大大提高了I期NSCLC的诊断能力。