Hepatocellular Carcinoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Lee Caroline
PROVIDER: E-GEOD-57958 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Methylation profiles reveal distinct subgroup of hepatocellular carcinoma patients with poor prognosis.
Mah Way-Champ WC Thurnherr Thomas T Chow Pierce K H PK Chung Alexander Y F AY Ooi London L P J LL Toh Han Chong HC Teh Bin Tean BT Saunthararajah Yogen Y Lee Caroline G L CG
PloS one 20140805 8
Hepatocellular Carcinoma (HCC) is one of the leading causes of cancer-associated mortality worldwide. However, the role of epigenetic changes such as aberrant DNA methylation in hepatocarcinogenesis remains largely unclear. In this study, we examined the methylation profiles of 59 HCC patients. Using consensus hierarchical clustering with feature selection, we identified three tumor subgroups based on their methylation profiles and correlated these subgroups with clinicopathological parameters. ...[more]
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Project description:Expression profiling of tumor and adjacent non-tumorous tissues of Hepatocellular Carcinoma (HCC) patients. Illumina HumanHT-12 V4.0 expression beadchip was used to obtain expression profiles across more than 31,000 annotated genes. Samples included 59 tumors and 59 adjacent non-tumorous samples. Total RNA obtained from the 39 tumors and 39 adjacent non-tumorous samples
2014-12-10 | E-GEOD-57957 | biostudies-arrayexpress
Project description:Disease relapse and resistance to chemotherapy represent challenging issues in a subset of Hodgkin Lymphoma (HL) patients. Activity and mechanism(s) of action of a novel PI3K/ERK dual inhibitor AEZS-136 (Ãterna Zentaris GmbH, Germany, EU) were examined in L-540, SUP-HD1, KM-H2 and L-428 cell lines. Despite exposure to AEZS-136 induced a significant cell growth inhibition (range, 30-80%), levels of caspase-independent cell death and mitochondrial dysfunction, were only observed in L-540 (62 ±9 vs 14 ±3%, P â¤.0001) and SUP-HD1 (46 ±2% vs 15 ±2%, P â¤.0001) cells. Gene expression profiling indicated that the effects of AEZS-136 treatment are associated with the modulation of cell cycle and cell death pathways. Exposure to AEZS-136 resulted in sustained production of reactive oxygen species (ROS) and activation of necroptotic cell death. The necroptosis inhibitor Necrostatin-1 prevented AEZS-136-induced ROS production, mitochondrial injury, activation of JNK and cell death. Knockdown experiments identified the immediate early response 3 (IER3) as a key signaling molecule that mediates AEZS-136-resistance to oxidative death of HL cells. Furthermore, in vivo xenograft studies demonstrated a 40-70% reduction in tumor burden (P < 0.0001) and a 10-fold increase in tumor necrosis in AEZS-136-treated animals compared to control mice. These data support further clinical evaluation of AEZS-136 in refractory/relapsed HL. The Hodgkin lymphoma cell lines were obtained from the DSMZ (Braunschweig, Germany, EU). Cells were routinely maintained in RPMI medium 1640 (Lonza, Basel, Switzerland) supplemented with 20% FBS (Lonza) and 2 mM glutamine (Lonza). Cells were maintained at 37°C in a water-saturated atmosphere of 5% CO2 in air. 4x106 HL cells were seeded in 75 cm2 flask and, after 24 hrs, cells were treated with 10 µM AEZS-136 (Aeterna Zentaris, Frankfurt, Germany, EU) in culture medium for 24 hours. At the end of treatment, cells were collected and RNA extracted.
2016-07-03 | E-GEOD-58899 | biostudies-arrayexpress
Project description:Background: How prenatal smoke exposure affects DNA methylation leading to atopic disorders remains to be addressed. Epigenetic biomarkers informative of prenatal smoke exposure and atopic disorders are wanting. Since most children suffering from atopic dermatitis (AD) continue to develop asthma later in life, we explored whether prenatal smoke exposure e induces DNA methylation and searched for predictive epigenetic biomarkers for smoke related atopic disorders. Methods: Methylation differences associated with smoke exposure were screened by Illumina methylation panel for children from the Taiwan birth panel study cohort initially. Information about development of atopic dermatitis (AD) and risk factors were collected. Cord blood cotinine levels were measured to represent prenatal smoke exposure. CpG loci that demonstrated a statistically significant difference in methylation were validated by methylation-dependent fragment separation (MDFS). Differential methylation in three genes (TSLP, GSTT1, and CYB5R3) was identified through the screen and their functions were investigated. Results: Among these, only thymic stromal lymphopoietin (TSLP) gene displayed significant difference in promoter methylation percentage after being validated by MDFS (p=0.029). TSLP gene was further investigated in a larger sample of 92 children from the cohort. Methylation status of the TSLP 5′-CpG island (CGI) was found to be significantly associated with prenatal smoke exposure (OR=3.59, 95%CI=1.49-8.64; cotinine level 0.10 ng/ml, sensitivity= 77%; specificity = 61%) and with AD (OR=4.77, 95%CI=1.47-15.53). The degree of TSLP 5′CGI methylation inversely correlated with TSLP protein expression levels (per unit: β=－6.69 ng/ml; 95% CIs, －12.80~－0.59; p=0.032). Conclusions: The effect of prenatal tobacco smoke exposure on the risk for AD may be mediated through DNA methylation. Cord blood methylated TSLP 5′CGI may be a potential epigenetic biomarker for environmentally-related atopic disorders. The buffy coat and plasma samples were separated and stored at −80°C. DNA (100 ng-500 ng) was extracted from cord white blood cells. Microarrays have been performed to investigate fourteen samples, which were classified as two groups according to cotinine exposure dosage (7 versus 7 : high exposure verses low exposure).
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2013-04-04 | E-GEOD-45198 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-04-04 | E-GEOD-45200 | biostudies-arrayexpress
Project description:We performed integrative methylation, gene dosage and expression profiling to explore the interplay between promoter methylation and loss in gene silencing at 3p11-p14 in cervical cancer. Totally 26 hypermethylated genes were identified by comparing the methylation level of individual CpG sites with corresponding data of normal cervical tissue. Candidate methylation regulated genes in tumors were proposed from the correlation between methylation and gene expression. Integrated analysis of methylation, gene dosage and expression revealed three significant regulation patterns encompassing 8 hypermethylated genes; a methylation driven pattern, a gene dosage driven pattern, and a combined methylation and gene dosage driven pattern. For the LRIG1 gene, patients with both hypermethylation and loss had a worse outcome compared to those harboring only hypermethylation or none of the events. C3orf14 emerged as a novel methylation regulated suppressor gene, for which knockdown was found to promote invasive growth in human papilloma virus (HPV)-transformed keratinocytes. Methylation levels from Illumina 450K methylation arrays were correlated with Illumina gene expression data in cohort 1 and validated in cohort 2.
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Project description:The recent discovery of mutations in metabolic enzymes has rekindled interest in harnessing the altered metabolism of cancer cells for cancer therapy. One potential drug target is isocitrate dehydrogenase 1 (IDH1) which is mutated in multiple human cancers. Here, we examine the role of mutant IDH1 in fully transformed cells with endogenous IDH1 mutations. A selective R132H-IDH1 inhibitor (AGI-5198) identified through a high-throughput screen dose-dependently blocked the ability of the mutant enzyme (mIDH1) to produce R-2-hydroxyglutarate (R-2HG). Under conditions of near complete R-2HG inhibition, the mIDH1 inhibitor induced demethylation of histone H3K9M3 and expression of genes associated with gliogenic differentiation. Blockade of mIDH1 impaired the growth of IDH1-mutant - but not IDH1-wildtype – glioma cells without appreciable changes in genome wide DNA methylation. These data suggest that mIDH1 may promote glioma growth through mechanisms beyond its well-characterized epigenetic effects. Samples were maintained in either DMSO or 1.5uM 5198 for 2 passages up to 20 passages. Biological replicates for each passage and treatment was collected and genomic DNA was extracted and analyzed on the Illumina 450K Methylation platform for a total of 16 samples.
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