Studying The Effect Of Epigenetic Gene Modification On Gastric Cancer Moleculor Mechanism Using Gene Chip Technique

Objective To Study the effect of epigenetic gene modification on gastric cancer moleculor mechanism. Methods 8 cases including tumor tissue and gastric mucosa tissue in gastric cancer patients were collected from 10.2007 to 01.2008. For the first time chromatin immunoprecipitation linked to microarrays (ChIP-chip) was adopted to profile the variations in histone H3K27me3 of Genome-wide in tumor tissue and gastric mucosa tissue. ChIP-qPCR was used to validate the microrray results. mRNA Expression analysis of 3 selected genes by qRT-PCR was performed to confirm the correlations between H3K27me3 and gene expression. Finally, DNA methylation of five selected genes was detected with MeDIP-qPCR. Results 227(67 increased and 160 decreased) gene displayed significant histone H3K27me3 difference were found in gastric cancer cell compared with gastric mucosa tissue. The results of ChIP-qPCR were coincided well with ChIP-chip. There was marked difference between tumor tissue and gastric mucosa tissue about mRNA expression of selected genens, so is DNA methylation. Conclusions Compared with gastric mucosa tissue, there are significant changes in tumor tissue about histone H3K27me3 profiling and DNA methylation level. It is feasble that ChIP-chip technique detects histone H3K27me3 level. Histone H3K27me3 probably bring gene expression about "silence effect". There is interaction between histone H3K27me3 and DNA methylation. But DNA methylation is probably more important than H3K27me3. Epigenetic gene modification probably plays an important role in gastric cancer moleculor mechanism. These novel candidate genes may be become potential biomarkers or future therapeutic targets. The ChIP-chip technique will help further reveal gastric cancer molecular mechanisms and discover new therapeutic targets.