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表观遗传修饰在人体细胞分化和适应环境上均发挥重要调控作用.一方面,细胞分化相关表观遗传非常稳定,具有明显的组织器官和细胞类型特异性;另一方面,机体对环境的适应性表观遗传则因环境因素不同而异,稳定性较低.这两类不同的表观遗传修饰在医学上具有不同的转化应用范围.恶性转化是机体组织中少数干细胞对环境致癌因素暴露做出的病理性适应反应的结果——细胞通过去分化重编程,获得无限制增殖和运动侵袭能力,同时拥有分化和适应性表观遗传变化特征.DNA甲基化变异的分析方法极其灵敏,可准确检出组织中少数细胞存在的变化,在识别癌前病变组织中的恶性转化细胞和肿瘤组织中的转移干细胞方面有重要应用前景.在前期研究中,我们已经证明肿瘤抑制基因p16甲基化失活可用作胃等器官上皮异型增生癌变的早期标志物.通过对胃癌发生发展相关DNA甲基化组扫描获得的90余个基因的DHPLC大规模验证,发现GFRA1的去甲基化激活、SRF和ZNF382的甲基化失活可用作胃癌等恶性肿瘤的转移标志物,已经在中、日、韩三国验证队列中得到证明;通过人群研究还发现血浆miR-221等含量的进行性升高可能是胃癌发生的预警信号.
Epigenetic modification plays an important regulatory role in human cell differentiation and adaptation to the environment.On the one hand, the epigenetic cell differentiation related to epigenetic stability is very stable, with obvious tissue and organ cell type specificity; the other hand, the body’s adaptation to the environment Sex epigenetic changes due to different environmental factors, the stability is low.The two different types of epigenetic modifications in the medical application of different transformation.Microscopic transformation is a small number of stem cells in the body tissue exposure to environmental carcinogens do The result of a pathological adaptive response - cells are reprogrammed by de-differentiation to gain unrestricted proliferation and motility, with both differentiated and adaptive epigenetic profiles. The analysis of DNA methylation variants is extremely sensitive and can be performed Accurate detection of the presence of a small number of cells in the tissue changes in the identification of precancerous lesions of malignant transformed cells and metastasis of tumor tissue has important application prospects.In the previous study, we have demonstrated the tumor suppressor gene p16 methylation Inactivation can be used as an early marker of dysplasia of the stomach and other epithelial dysplasia. Through the development of gastric cancer DNA methylation group scans of more than 90 large-scale DHPLC gene validation and found GFRA1 demethylation activation, SRF and methylation of ZNF382 inactivation can be used as a marker of metastasis of gastric cancer and other malignancies have been China, Japan and South Korea have been demonstrated in the validation cohort. Through population studies, we also found that the progressive increase of plasma miR-221 content may be an early warning signal for the occurrence of gastric cancer.