In total, for survival selleck chemical Veliparib analyses we studied 16 distinct types of cancer. Details of each dataset, the number of samples with clinical details, the expression platform, and associated Pubmed IDs for the GEO datasets are in Additional file 13 Table S3. Gene expression microarray analysis Generation of Gene Expression Microarrays was previously described and data were deposited in Inhibitors,Modulators,Libraries ArrayExpress database. Gene Set Enrichment Analysis measures the enrich ment of a gene set within a GEM experiment. The enrich ment score is a metric Inhibitors,Modulators,Libraries Inhibitors,Modulators,Libraries of the skew of a gene set within the rank of genes sorted by their GEM expression difference. The significance of enrichment is the proportion of true ES 1000 ES generated from random gene sets. Leading edge genes are the subset that contributes most to the ES.

Statistical analysis For Inhibitors,Modulators,Libraries survival analysis we used the R survival package. To survey for potential association between gene expression and survival we categorized samples as below or above median expression for each gene and then calculated the log rank P value comparison between the groups. For KIRC, SKCM and PRAD GSE21034 datasets with significant NFE2L2 log rank tests we also calculated the hazard ratio using the Cox proportional hazard model. Elsewhere data were analyzed using Students t test, Spearmans rho or log rank test as appropriate for the analysis. Values are given as mean SD. All statistical tests were two sided, and results were considered statistically sig nificant when P 0. 05. Background Prostate cancer is the most common non cutaneous malignancy in men in the Western world.

The etiology of prostate cancer is not well defined. however, the inhibition of various tumor suppressor genes and con comitant activation of oncogenes is a frequent occur rence in most cancers, including prostate cancer. DNA hypermethylation of promoters at CpG sequences often sterically hinders the binding of transcription factors, thereby represses gene Inhibitors,Modulators,Libraries transcription. The transfer of a methyl group to DNA at the fifth carbon position of cytosine residues by the DNA methyltransferase family of enzymes is one of the most common events for the establishment of epigenetic program. Three active DNMTs have been identified so far in mammalian cells. DNMT1, DNMT3A, and DNMT3B. DNMT1 is the most abundant and methylates hemimethylated CpG di nucleotides in the mammalian genome during DNA replication in a number of different cancer types.

DNMT3A and DNMT3B are methyltransferases involved in de novo methylation of DNA following replication. Numerous reports things have demonstrated the overexpres sion of DNMT1 in lung, hepatocellular, acute and chronic myelogenous leukemia, colorectal, gastric, breast and prostate cancers. Gravina and associates have shown that the hormone resistant prostate cancer phenotype is associated with an increase in DNMT expression and activity.