高低转移大细胞肺癌细胞株L9981和NL9980间甲基化差异基因的初步研究

Methylation Profile Difference in Human High-metastatic Large Cell Lung Cancer Cell Line L9981 and Low-metastatic Large Cell Lung Cancer Line NL9980

背景与目的肺癌是人类肿瘤中最容易发生侵袭转移的恶性肿瘤之一。影响肺癌患者预后及生存的最主要因素是远处转移。本文旨在分析具有相似遗传背景和不同转移潜能的人大细胞肺癌细胞株间基因甲基化的差异,为深入研究肿瘤转移机制提供充分的目标基因选择和发现肿瘤相关的新基因的机会。方法应用全基因组甲基化芯片杂交技术分析具有相同遗传背景和不同转移潜能的人大细胞肺癌细胞株L9981和NL9980之间差异甲基化基因,并运用生物信息学的方法分析这些差异基因。结果与NL9980相比,在L9981细胞株中有1552个高甲基化DNA片断共涉及735个基因,其中656个已知基因及79个未知基因。低甲基化DNA片段1787个,涉及809个基因,其中698个已知基因及111个未知基因。这些基因涉及细胞生物进程及其调节、基因表达、信号传导、细胞通讯、细胞运动、细胞粘附及血管生成等。结论抑癌基因及信号通路负向调节基因的高甲基化及癌基因、细胞粘附因子的低甲基化可能与L9981的侵袭性及克隆能力强有关。

Background and objective Invasion and metastasis is one of malignant phenotype of lung cancer and the important cause of the death of lung cancer patients.The aim of this study is to explore the methylation profile difference in different metastatic potential cell lines.Methods To compare the DNA methylation profile of two large cell lung cancer cell lines with different metastatic potential by MeIP chip hybridization,hypermethylated and hypomethylated genes of L9981 cell lines were analyzed online in NIH-DAVID,KEGG and MILANO webside.Results Compared with NL9980 cell line,735 genes are hypermethylated in L9981,including 656 known genes and 79 unknown genes;809 gene are hypermethylated in L9981,including 698 known genes and 111 unknown genes;the different genes are involved in cell process,signal transduction,cell communication,cell adhesion,cell motility,and angiogenesis.Conclusion Hypermethylation of suppressor genes and negative regulator of signal transduction and hopomethylation of oncogene and cell adhesion molecules （CAMs） in L9981 may promote metastasis of tumor cells.