肺癌的发病率和病死率居全球恶性肿瘤首位,严重地危害着人类健康。在哺乳动物细胞中，特定基因CpG岛DNA甲基化修饰是一种重要的表观遗传学修饰方式。DNA甲基化修饰是指在DNA甲基转移酶(DNA methyltransferase，DNMT) 催化下， S2腺苷甲硫氨酸（S2 adenosylmethionine, SAM）作为甲基供体将甲基转移到胞嘧啶上的过程。基因启动子的DNA甲基化修饰阻碍RNA聚合酶与之结合，从而调控该基因转录的频率和水平。在肿瘤细胞中存在某些关键基因甲基化异常现象，异常的甲基化修饰与肿瘤的发生和进展密切相关。非小细胞肺癌（non-small cell lung cancer， NSCLC)组织中，FAM19A4、GATA5、SOX17、CDO1、ZFP42、TAC1、FHIT和MGMT等基因启动子区域CpG岛高甲基化，抑制了抑癌基因启动子的转录，从而导致基因沉默，促进了肺癌的发展。这些基因的甲基化状态改变有希望发展成为肺癌特异性的标志物。

为了筛选和确定肺癌甲基化标志物，主要研究手段包括逆转录PCR（reverse transcription-PCR, RT-PCR）、定量PCR(quantitative PCR, qPCR)、甲基化特异性PCR(methylation-specific PCR, MS-PCR)，以及肿瘤免疫组化技术。肺癌组织中甲基化差异性较大且表达显著的基因位点有可能成为肺癌候选标志物，用于肺癌早期诊断、药物敏感性预测，以及临床预后评估等。

本论文将综述DNA甲基化在肺癌中的研究进展，主要内容包括： 1）非小细胞肺癌中DNA甲基化过程与基因表达调控；2）DNA 启动子CpG岛甲基化检测方法；3）DNA甲基化检测在非小细胞肺癌临床诊断和预后中的应用；4）DNA去甲基化药物在非小细胞肺癌临床治疗中的应用；5）DNA甲基化检测方法展望。

本论文也初步分析了非小细胞肺癌相关基因的转录表达水平，为肺癌样本的甲基化分析提供了基础。

The incidence and mortality of lung cancer ranks first in the world of malignant tumors, which seriously endangers human health. DNA methylation modification is an important epigenetic modification method. DNA methylation modification refers to the process of S2 adenosylmethionine (SAM) as a methyl donor to transfer methyl to cytosine under the catalysis of DNA methyltransferase (DNMT). DNA methylation modification of the gene promoter prevents RNA polymerase from binding to it, thereby regulating the frequency and level of transcription of the gene. There are abnormal methylation of certain key genes in tumor cells. Abnormal methylation modification is closely related to tumor occurrence and progression. In non-small cell lung cancer (NSCLC) tissues, CpG islands in gene promoter regions such as FAM19A4， GATA5, SOX17, CDO1, ZFP42, TAC1, FHIT and MGMT showed hypermethylation , suppresses the transcription of the tumor suppressor gene promoter, resulting in gene silencing and promoting the development of lung cancer. Changes in the methylation status of these genes are expected to develop into lung cancer-specific markers.

In order to screen and determine lung cancer methylation markers, the main research methods include reverse transcription PCR (RT-PCR), quantitative PCR (quantitative PCR, qPCR), methylation-specific PCR MS-PCR) and tumor immunohistochemistry. Gene sites with large differences in methylation and significant expression in lung cancer tissues may become lung cancer candidate markers for early diagnosis of lung cancer, drug sensitivity prediction and clinical prognosis assessment.

This paper will review the research progress of DNA methylation in lung cancer. The main contents include: 1) DNA methylation process and gene expression regulation in lung cancer; 2) Detection method of DNA promoter CpG island methylation; 3) Application of DNA methylation detection in the diagnosis and prognosis of non-small cell lung cancer; 4) Application of DNA demethylation drugs in clinical treatment of non-small cell lung cancer；5) Outlook of DNA methylation detection methods.

This paper also preliminarily analyzed the transcript expression level of non-small cell lung cancer related genes, which provided a basis for the methylation analysis of lung cancer samples.