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Chromatin Immunoprecipitation ChIP to Assay Dynamic Histone Modification in Activated Gene Expression in Human Cells
Published on: July 29, 2010
Comprehensive analysis of histone modification-associated genes on differential gene expression and prognosis in
Xiangyu Meng1, Yan Zhao1, Jingwei Liu2
1Department of Gastric Surgery, Cancer Hospital of China Medical University/Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China.
Abstract:
Accumulating evidence suggests that the epigenetic alterations caused by histone modifications have important roles in the genesis of gastric cancer (GC), particularly the well-studied acetylation and methylation modifications. In the present study, a Bioinformatics analysis of the expression of histone modification-associated genes in GC and normal tissues was performed by using datasets from Oncomine, the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). The clinical data of GC patients were downloaded from TCGA to determine the association between histone modification-associated gene expression and clinicopathological parameters or survival of GC. Finally, lysine acetyltransferase 2A (KAT2A), nuclear receptor coactivator 1 (NCOA1), SMYD family member 5 (SMYD5), protein arginine methyltransferase 1 (PRMT1) and PRDF1-RIZ (PR)/Su(var)3-9, enhancer-of-zeste and trithorax (SET) domain 16 (PRDM16) were screened; KAT2A, SMYD5 and PRMT1 were upregulated, while PRDM16 expression was downregulated in GC. Analysis of the GEO and Oncomine datasets revealed that NCOA1 was upregulated, which was contrary to the result obtained with the TCGA stomach adenocarcinoma dataset. Aberrant expression of KAT2A, NCOA1, SMYD5 and PRMT1 was more obvious in gastric intestinal-type adenocarcinoma; low NCOA1 expression was associated with better overall survival of GC patients [hazard ratio (HR)=0.690, 95% CI=0.570-0.840, P<0.001] and was an independent predictor for patients diagnosed with GC (HR=0.639, 95% CI=0.437-0.933, P=0.020). Correlation analysis and protein-protein interaction network analysis indicated a close association between ATAD2 and estrogen receptor 1 (ESR1), PRMT1, NCOA1 and KAT2A. In conclusion, differential expression of KAT2A, NCOA1, SMYD5, PRMT1 and PRDM16 was identified in GC vs. normal tissues, low NCOA1 expression was associated with poor survival of GC and ATAD2 may interact with ESR1 to regulate NCOA1 and PRMT1 in GC.
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