Genome-wide DNA methylation profiles of hepatocellular carcinoma
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PROVIDER: PRJNA760921 | ENA |
REPOSITORIES: ENA
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Project description:Alcohol is a major risk factor for hepatocellular carcinoma (HCC) although the mechanisms underlying the alcohol-related liver carcinogenesis are still poorly understood. Alcohol is known to increase hepatocarcinogenesis possibly by inducing aberrant DNA methylation through the reduced provision of methyl groups within the hepatic one-carbon metabolism. Whether the epigenetically-regulated pathways in alcohol-associated HCC can be reversible or modifiable by nutritional factors is unknown. The aim of the present study was to investigate the genome wide promoter DNA methylation profiles along with array-based, gene expression profiles in non-viral, alcohol-associated HCC. From eight HCC patients the methylation status and transcriptional levels of all annotated genes were compared by analyzing HCC tissue and the cancer-free surrounding liver tissue, following curative surgery. After merging both the DNA methylation and gene expression data, we identified 159 hypermethylated-repressed, 30 hypomethylated-induced, 49 hypermethylated-induced and 56 hypomethylated-repressed genes. A number of potentially novel candidate tumor-suppressor genes (FAM107A, IGFALS, MT1G, MT1H, RNF180) demonstrated promoter hypermethylation and transcriptional repression in alcohol-associated HCC. Notably, promoter DNA methylation appeared as the regulatory mechanism for the transcriptional repression of genes controlling the retinol metabolic pathway (ADH1A, ADH1B, ADH6, CYP3A43, CYP4A22, RDH16) and SHMT1, a key gene within one-carbon metabolism. A genome-wide DNA methylation approach linked up with array-based gene expression profiles allowed identifying a number of novel, epigenetically-regulated candidate tumor-suppressor genes in alcohol-associated hepatocarcinogenesis. Retinol metabolism genes and SHMT1 are also epigenetically-regulated through promoter DNA methylation in alcohol-associated hepatocarcinogenesis. 16 samples (8 control samples from non-neoplastic liver tissue, 8 test samples from hepatocellular carcinoma) from 8 patients affected from hepatocellular carcinoma were analyzed.
2015-05-05 | E-GEOD-59260 | biostudies-arrayexpress
Project description:Introduction: Hepatocellular carcinoma (HCC) is one of the most aggressive solid tumors and oncogenic pathways (e.g Akt, IGF signaling) are often activated in high proliferating HCC. Among several genetic alterations, epigenetic changes seem to be involved in the development and progression of HCC. DNA hypermethylation of promoter regions is almost always associated with transcriptional silencing and can lead to inactivation of tumor suppressor genes (TSG) in cancer cells. Aim: (1) To identify genes differently methylated in a subclass of HCC associated with proliferation and, (2) To correlate methylation changes with activation of molecular pathways. Methods: gDNA of 20 HCC, 8 cirrhotic and 8 normal liver samples was extracted and the methylation status was detected by the Illumina HumanMethylation27 BeadChip and immunohistochemistry of p-AKT, pIGF IR, p-S6 was analyzed. Results: Unsupervised clustering clearly classified normal livers, cirrhosis and HCC in 3 different groups. 961 genes were significantly hypermethylated in HCC compared to cirrhotic and 3942 genes showed hypermethylation in cirrhotic compared to normal liver tissue. 163 genes showed stepwise significant hypermethylation from normal to cirrhotic to HCC, including well described (p16, SOCS2, SFRP5, RBP1) and potential (SRD5A2, PCDH8, IGF-1R, UCHL1) TSGs, and the miR-10a. 133 genes were specifically hypermethylated in HCC. Among them the transcription factors GATA2, DLX1, and KLF14, all significantly inversely correlated to gene expression (p=0.003, p=0.03, and p=0.007, respectively). The methylation status of SOCS2 (p=0.025) and DLX1 (p=0.025) was significantly correlated to phosphorylation of IGFR1. Samples with RBP1 hypermethylation showed significantly higher AFP serum levels (p=0.018). Conclusion: Whole genome methylation analysis markedly classifies normal, cirrhotic and HCC samples. 8 TSGs play a key role in this stepwise progression of hypermethylation in the development of HCC and could be a promising point of action in anticancer therapy. Genomic DNA extracted from fresh frozen tissue specimens and cell lines was hybridized to genome-wide mthylation beadarray after bisulphite treatment. Keywords: DNA methylation, hepatocellular carcinoma, tissue, cell line
2013-09-27 | E-GEOD-44970 | biostudies-arrayexpress
Project description:Genome-wide DNA methylation profiling was performed in samples of cancerous tissue obtained from patients with hepatocellular carcinomas using the Illumina Infinium HumanMethylation450 Beadchip.
2022-01-17 | GSE183468 | GEO
Project description:Genome-wide expression analysis of 228 hepatocellular carcinoma and 168 cirrhotic samples as part of a integrated study of gene expression and DNA-methylation de-regulation in patients with hepatocellular carcinoma Analysis of whole-genome transcriptome changes in human samples from hepatocellular carcinoma patients
2015-03-07 | GSE63898 | GEO
Project description:DNA methylation profiling of tumor and adjacent non-tumorous tissues of Hepatocellular Carcinoma (HCC) patients. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs. Samples included 59 tumors and 59 adjacent non-tumorous samples.
2014-12-10 | GSE57956 | GEO
Project description:Alcohol is a major risk factor for hepatocellular carcinoma (HCC) although the mechanisms underlying the alcohol-related liver carcinogenesis are still poorly understood. Alcohol is known to increase hepatocarcinogenesis possibly by inducing aberrant DNA methylation through the reduced provision of methyl groups within the hepatic one-carbon metabolism. Whether the epigenetically-regulated pathways in alcohol-associated HCC can be reversible or modifiable by nutritional factors is unknown. The aim of the present study was to investigate the genome wide promoter DNA methylation profiles along with array-based, gene expression profiles in non-viral, alcohol-associated HCC. From eight HCC patients the methylation status and transcriptional levels of all annotated genes were compared by analyzing HCC tissue and the cancer-free surrounding liver tissue, following curative surgery. After merging both the DNA methylation and gene expression data, we identified 159 hypermethylated-repressed, 30 hypomethylated-induced, 49 hypermethylated-induced and 56 hypomethylated-repressed genes. A number of potentially novel candidate tumor-suppressor genes (FAM107A, IGFALS, MT1G, MT1H, RNF180) demonstrated promoter hypermethylation and transcriptional repression in alcohol-associated HCC. Notably, promoter DNA methylation appeared as the regulatory mechanism for the transcriptional repression of genes controlling the retinol metabolic pathway (ADH1A, ADH1B, ADH6, CYP3A43, CYP4A22, RDH16) and SHMT1, a key gene within one-carbon metabolism. A genome-wide DNA methylation approach linked up with array-based gene expression profiles allowed identifying a number of novel, epigenetically-regulated candidate tumor-suppressor genes in alcohol-associated hepatocarcinogenesis. Retinol metabolism genes and SHMT1 are also epigenetically-regulated through promoter DNA methylation in alcohol-associated hepatocarcinogenesis.
2015-05-05 | GSE59260 | GEO
Project description:DNA methylation profiling of tumor and adjacent non-tumorous tissues of Hepatocellular Carcinoma (HCC) patients. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs. Samples included 59 tumors and 59 adjacent non-tumorous samples. Bisulphite converted DNA from the 59 tumors and 59 adjacent non-tumorous samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip.
2014-12-10 | E-GEOD-57956 | biostudies-arrayexpress
Project description: Not available
| S-DIXA-D-1150 | biostudies-other
Project description:Genome-wide DNA methylation profiling was performed in peripheral leukocytes to identify biomarkers that could track hepatitis B progression to hepatocellular carcinoma (HCC). Samples included 48 HBsAg carriers who developed HCC and 48 HBsAg carriers who did not during follow-up.
2019-03-04 | GSE78904 | GEO
Project description:Introduction: Hepatocellular carcinoma (HCC) is one of the most aggressive solid tumors and oncogenic pathways (e.g Akt, IGF signaling) are often activated in high proliferating HCC. Among several genetic alterations, epigenetic changes seem to be involved in the development and progression of HCC. DNA hypermethylation of promoter regions is almost always associated with transcriptional silencing and can lead to inactivation of tumor suppressor genes (TSG) in cancer cells. Aim: (1) To identify genes differently methylated in a subclass of HCC associated with proliferation and, (2) To correlate methylation changes with activation of molecular pathways. Methods: gDNA of 20 HCC, 8 cirrhotic and 8 normal liver samples was extracted and the methylation status was detected by the Illumina HumanMethylation27 BeadChip and immunohistochemistry of p-AKT, pIGF IR, p-S6 was analyzed. Results: Unsupervised clustering clearly classified normal livers, cirrhosis and HCC in 3 different groups. 961 genes were significantly hypermethylated in HCC compared to cirrhotic and 3942 genes showed hypermethylation in cirrhotic compared to normal liver tissue. 163 genes showed stepwise significant hypermethylation from normal to cirrhotic to HCC, including well described (p16, SOCS2, SFRP5, RBP1) and potential (SRD5A2, PCDH8, IGF-1R, UCHL1) TSGs, and the miR-10a. 133 genes were specifically hypermethylated in HCC. Among them the transcription factors GATA2, DLX1, and KLF14, all significantly inversely correlated to gene expression (p=0.003, p=0.03, and p=0.007, respectively). The methylation status of SOCS2 (p=0.025) and DLX1 (p=0.025) was significantly correlated to phosphorylation of IGFR1. Samples with RBP1 hypermethylation showed significantly higher AFP serum levels (p=0.018). Conclusion: Whole genome methylation analysis markedly classifies normal, cirrhotic and HCC samples. 8 TSGs play a key role in this stepwise progression of hypermethylation in the development of HCC and could be a promising point of action in anticancer therapy.
2013-09-27 | GSE44970 | GEO