Epigenetic changes are potentially important for the ontogeny and progression of tumors but are not usually studied because of the complexity of analyzing transcript regulation resulting from epigenetic alterations.Pr...Epigenetic changes are potentially important for the ontogeny and progression of tumors but are not usually studied because of the complexity of analyzing transcript regulation resulting from epigenetic alterations.Prostate cancer(PCa)is characterized by variable clinical manifestations and frequently unpredictable outcomes.We performed an expression quantitative trait loci(eQTL)analysis to identify the genomic regions that regulate gene expression in PCa and identified a relationship between DNA methylation and clinical information.Using multi-level information published in The Cancer Genome Atlas,we performed eQTL-based analyses on DNA methylation and gene expression.To better interpret these data,we correlated loci and clinical indexes to identify the important loci for both PCa development and progression.Our data demonstrated that although only a small proportion of genes are regulated via DNA methylation in PCa,these genes are enriched in important cancer-related groups.In addition,single nucleotide polymorphism analysis identified the locations of CpG sites and genes within at-risk loci,including the 19q13.2-q13.43 and 16q22.2-q23.1 loci.Further,an epigenetic association study of clinical indexes detected risk loci and pyrosequencing for site validation.Although DNA methylation-regulated genes across PCa samples are a small proportion,the associated genes play important roles in PCa carcinogenesis.展开更多
基金the Projects of National Science Foundation of China(No.81070600 and 81570684)Projects of the Shanghai Committee of Science and Technology,China(No.14430720800,134119a0600,and 11ZR1424100).
文摘Epigenetic changes are potentially important for the ontogeny and progression of tumors but are not usually studied because of the complexity of analyzing transcript regulation resulting from epigenetic alterations.Prostate cancer(PCa)is characterized by variable clinical manifestations and frequently unpredictable outcomes.We performed an expression quantitative trait loci(eQTL)analysis to identify the genomic regions that regulate gene expression in PCa and identified a relationship between DNA methylation and clinical information.Using multi-level information published in The Cancer Genome Atlas,we performed eQTL-based analyses on DNA methylation and gene expression.To better interpret these data,we correlated loci and clinical indexes to identify the important loci for both PCa development and progression.Our data demonstrated that although only a small proportion of genes are regulated via DNA methylation in PCa,these genes are enriched in important cancer-related groups.In addition,single nucleotide polymorphism analysis identified the locations of CpG sites and genes within at-risk loci,including the 19q13.2-q13.43 and 16q22.2-q23.1 loci.Further,an epigenetic association study of clinical indexes detected risk loci and pyrosequencing for site validation.Although DNA methylation-regulated genes across PCa samples are a small proportion,the associated genes play important roles in PCa carcinogenesis.