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MRNA/microRNA expression profiles of HCC or CCC patients' liver, together with those of non-tumor part tissues

ABSTRACT: 11 CCC and 5 HCC patients' tumor and non-tumor parts tissues are extracted. Then total RNA are purified from tissues and mRNA and miRNA profiles are measured using agilent one color microarrays designed for mRNA or microRNA expression profiles.

ORGANISM(S): Homo sapiens

PROVIDER: GSE57555 | GEO | 2015/12/21

SECONDARY ACCESSION(S): PRJNA246722

REPOSITORIES: GEO

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mRNA/microRNA expression profiles of HCC or CCC patients' liver, together with those of non-tumor part tissues

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Project description:Targeted approaches have revealed frequent epigenetic alterations in ovarian cancer, but the scope and relation of these changes to histologic subtype of disease is unclear. Genome-wide methylation and expression data for 14 clear cell carcinoma (CCC), 32 non-CCC, and 4 corresponding normal cell lines were generated to determine how methylation profiles differ between cells of different histological derivations of ovarian cancer. Consensus clustering showed that CCC is epigenetically distinct. Inverse relationships between expression and methylation in CCC were identified, suggesting functional regulation by methylation, and included 22 hypomethylated (UM) genes and 276 hypermethylated (HM) genes. Categorical and pathway analyses indicated that the CCC-specific UM genes were involved in response to stress and many contain hepatocyte nuclear factor (HNF) 1 binding sites, while the CCC-specific HM genes included members of the estrogen receptor alpha (ERalpha) network and genes involved in tumor development. We independently validated the methylation status of 17 of these pathway-specific genes, and confirmed increased expression of HNF1 network genes and repression of ERalpha pathway genes in CCC cell lines and primary cancer tissues relative to non-CCC specimens. Treatment of three CCC cell lines with the demethylating agent Decitabine significantly induced expression for all five genes analyzed. Coordinate changes in pathway expression were confirmed using two primary ovarian cancer datasets (p<0.0001 for both). Our results suggest that methylation regulates specific pathways and biological functions in CCC, with hypomethylation influencing the characteristic biology of the disease while hypermethylation contributes to the carcinogenic process.

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Homo sapiens

Project description:mRNA/microRNA expression profiles of HCC or CCC patients' liver, together with those of non-tumor part tissues

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