中文摘要：

DNA甲基化是影响基因表达的重要因素之一。DNA甲基化芯片已广泛应用于寻找癌症的标志物,但是目前还没有研究对这些标志物的重复性进行评价。另外,DNA甲基化对基因表达的影响也存在争议。在本文中,通过分析肾细胞癌的两套甲基化数据,发现它们的差异甲基化基因的方向高度的一致,证明通过甲基化芯片获得的甲基化标记有很高的重复性。进一步分析甲基化基因对应的表达改变,发现肾细胞癌中高甲基化的基因显著影响表达下调,而低甲基化的基因与表达改变无显著关系。最后,通过功能分析,找到了三个同时发生甲基化和表达改变的通路。针对这些通路研究DNA甲基化抑制剂,可能有助于肾细胞癌的靶向治疗。

英文摘要：

DNA methylation is an important cause of altered gene expression and found in many human cancers.Although the DNA methylation microarrays were widely used in cancer research,the consistency of signatures from different studies was not assessed.Also the inverse correlation between methylation and expression change was arguable.Here,using two methylation datasets of kidney renal cell carcinoma,we found the methylation changes were highly consistent across different datasets,suggesting methylation change detected from methylation microarrays were reproducible.Then by gene expression data of kidney renal cell carcinoma,we found hypermethylated genes were significantly down-regulated while hypomethylated genes were not related to expression change.Finally,we found three pathways which simultaneously showed methylation and expression change.These pathways may be helpful for mechanism research and target therapy of kidney renal cell carcinoma.