Profiling of exome mutations associated with progression of HBV-related hepatocellular carcinoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Hyun Goo Woo
PROVIDER: E-GEOD-62441 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:We profiled the mutations and gene expressions of early and advanced hepatocellular carcinoma (HCC) related with Hepatitis B-viral infection. Integrative analysis was performed with whole-exome sequencing and gene expression profiles of the 12 cases of early and advanced HCCs and paired non-tumoral adjacent liver tissues.
2014-10-19 | GSE62441 | GEO
Project description:Although senescence has long been implicated in aging-associated pathologies, it is not clearly understood how senescent cells are linked to these diseases. To address this knowledge gap, we profiled cellular senescence phenotypes and mRNA expression patterns during replicative senescence in human diploid fibroblasts. We identified a sequential order of gain-of-senescence phenotypes: low levels of reactive oxygen species, cell mass/size increases with delayed cell growth, high levels of reactive oxygen species with increases in senescence-associated M-NM-2-galactosidase activity (SA-M-NM-2-gal), and high levels of SA-M-NM-2-gal activity. Gene expression profiling revealed four distinct modules in which genes were prominently expressed at certain stages of senescence, allowing us to divide the process into four stages: early, middle, advanced, and very advanced. Interestingly, the gene expression modules governing each stage supported the development of the associated senescence phenotypes. Senescence-associated secretory phenotype-related genes also displayed a stage-specific expression pattern with three unique features during senescence: differential expression of interleukin isoforms, differential expression of interleukins and their receptors, and differential expression of matrix metalloproteinases and their inhibitory proteins. The analysis of time series gene expression level during replicaive senescence.
2013-04-24 | E-GEOD-41714 | biostudies-arrayexpress
Project description:Non-melanoma skin cancers (NMSC) including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are more common kinds of skin cancer. Although these tumors share common pathological and clinical features, their similarity and heterogeneity at molecular levels are not fully elaborated yet. Here, by performing comparative analysis of gene expression profiling of BCC, SCC, and normal skin tissues, we could classify the BCC into three subtypes of classical, SCC-like, and normal-like BCCs. Functional enrichment and pathway analyses revealed the molecular characteristics of each subtype. The analysis of gene expression profiling among non-melanoma skin cancer types
2014-12-13 | E-GEOD-53462 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) affects millions of people worldwide and is a lethal malignancy for which there are no effective therapies. To identify prognostic gene markers for liver cancer, we conducted transcriptome profiling of frozen tissues (tumor and non-tumor) from 300 early-to-advanced stage HCCs plus 40 cirrhotic and 6 normal livers. We have profiles 268 HCC tumor, 243 adjacent non-tumor, 40 cirrhotic and 6 healthy liver samples.
2011-07-05 | E-GEOD-25097 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) affects millions of people worldwide and is a lethal malignancy for which there are no effective therapies. To identify prognostic gene markers for liver cancer, we conducted transcriptome profiling of frozen tissues (tumor and non-tumor) from 300 early-to-advanced stage HCCs plus 40 cirrhotic and 6 normal livers.
2011-07-05 | GSE25097 | GEO
Project description:To characterize the genetic alterations that instigate hepatitis C virus-induced hepatocellular carcinoma (HCC), we conducted an integrative genomic analysis of 103 HCCs. Most tumors harbored 1q gain, 8q gain or 8p loss, with occasional alterations in 13 additional chromosome arms. In addition to amplifications at 11q13 in 6 tumors, 4 tumors harbored focal gains at 6p21 incorporating VEGFA, which were confirmed in 4 of 113 HCC in an independent validation set. Strikingly, this locus overlapped with copy gains in 4 of 371 lung adenocarcinomas. Overexpression of VEGFA via 6p21 gain suggested a cell-nonautonomous mechanism of oncogene activation. Hierarchical clustering of gene expression among 91 tumors identified 5 classes, including ‘Wnt-CTNNB1’, ‘proliferation’ and ‘interferon-related’ gene classes. We also discovered a novel class defined by polysomy of chromosome 7, gains of which were associated with early tumor recurrence after resection. These findings reveal key alterations in HCC pathogenesis and implicate potential therapeutic targets. Keywords: disease state analysis 103 hepatocellular carcinomas and 95 adjacent cirrhotic, non-tumoral liver tissue were obtained at the time of surgical resection of orthotopic transplantation.
2008-06-21 | E-GEOD-9845 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) is one of the most common causes of death worldwide and the fourth most prevalent type of cancer. Whereas curative treatments such as liver transplantation, ablation or surgery are optimal for early stages, only paliative treatments are given to intermediate and advanced stages of the disease. Despite the introduction of immune regulators as first-line treatments for advanced stages, Sorafenib is still the standard of care in the clinical practice. In cell lysates, anti-tumoral properties of Sorafenib were related to upregulation of miR-200c-3p (anti-tumoral miRNA) at 6 hours of treatment and downregulation of miR-222-5p and miR-512-3p (pro-tumoral miRNAs) at 24 hours. We have identified these miRNA biomarkers of Sorafenib treatment response in plasma of patients with advanced HCC treated with Sorafenib. In particular, miR-200c-3p has been related to increased survival benefit whereas miR-222-5p and miR-512-3p have been related to worse prognosis. Our study has sequenced HepG2 cells treated with Sorafenib and miR-200c-3p inhibitor, and transfected with miR-222-5p and miR-512-3p mimics to unravel the molecular pathways governing Sorafenib response
2022-04-28 | GSE201695 | GEO
Project description:Five matching sets of non-malignant liver tissues and HCCs from individuals chronically infected with hepatitis B virus (HBV) were examined. The HBV genomic sequences were determined using overlapping PCR amplicons covering the entire viral genome. Four pairs of tissues were infected with HBV of genotype C, while one pair - with genotype B. HBV replication markers were found in all tissues. In majority of HCC samples, the levels of pre-genomic/pre-core RNA (pgRNA) and covalently closed circular DNA (cccDNA) were lower than those of liver tissue counterparts. Regardless of the presence of HBV replication markers, (i) integrant-derived HBV RNAs (id-RNAs) were found using RT-PCR analysis in all tissues, and were considerably abundant or predominant in 6/10 tissue samples (2 livers and 4 HCCs); (ii) the RNAs that were polyadenylated using cryptic HBV polyadenylation signal and therefore could be produced by HBV replication or derived from integrated HBV DNA were found in 5/10 samples (3 livers and 2 HCCs), and were considerably abundant species in 3/10 tissues (2 livers and 1 HCC); and (iii) cccDNA-transcribed RNAs polyadenylated near position 1931 were not abundant in 7/10 tissues (2 livers and 5 HCCs), and were predominant only in two livers. Subsequent RNA sequencing analysis of selected liver/HCC samples also showed relative abundance of id-RNAs in most of examined tissues. Our findings suggesting that id-RNAs could represent a significant source of HBV envelope proteins, which is independent of viral replication, are discussed in the context of possible contribution of id-RNAs to the HBV life cycle.
2021-02-06 | GSE110345 | GEO
Project description:To compare the characteristics and mechanisms of Myc and xmrk induced zebrafish liver tumor, next generation sequencing-based SAGE analyses were used to examine the transcriptomes of tumor and control samples. The results indicated that relatively small overlaps of significantly deregulated genes and biological pathways among different zebrafish liver tumor models.Nevertheless, they all significantly correlate with advanced or very advanced human hepatocellular carcinoma (HCC). Molecular signature from each oncogene-induced zebrafish liver tumor correlated with only a small subset of human HCC samples, and they share conserved up-regulated pathways. A short list of commonly deregulated genes among different zebrafish liver tumors showed accordant deregulation in the majority of human HCCs, suggesting that they may serve as common diagnosis markers and therapeutic targets.Thus, these transgenic zebrafish models with well-defined oncogene-induced tumors are valuable tools for molecular classification of human HCCs and for understanding of molecular drivers in hepatocarcinogenesis in each human HCC subgroup. Transcriptome profiling of Myc tumor sample (X-M+D+) and control samples (X-M-D-, X-M+D-, X-M-D+), xmrk tumor sample (X+M-D+) and control samples (X-M-D-, X+M-D-, X-M-D+), were generated by deep sequencing, using 3' RNA-SAGE on SOLiD system
2013-12-17 | E-GEOD-53342 | biostudies-arrayexpress
Project description:Activation of Wnt/β-catenin signaling is frequent in human and rodent hepatocarcinogenesis. Although in mice, the tumor promoting activity of agonists of constitutive androstane receptor (CAR) occurs via selection of carcinogen-initiated cells harbouring β-catenin mutations, the molecular alterations leading to hepatocellular carcinoma (HCC) development by The CAR agonist 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), in the absence of genotoxic injury are unknown. Here we show that CAR activation per se induced HCC in mice and that 91% of them carried β-catenin point mutations or large in-frame deletions/exon skipping targeting Ctnnb1 exon 3. Point mutations in HCCs induced by TCPOBOP alone displayed different nucleotide substitutions compared to those found in HCCs from mice pre-treated with diethylnitrosamine (DENA). Moreover, unlike those occurring in HCCs from DENA+TCPOBOP mice, they did not result in increased expression of β-catenin target genes, such as Glul, Lgr5, Rgn, Lect2 and Ccnd1, or nuclear translocation of β-catenin when compared to the control liver. Remarkably, in the non-tumoral liver tissue, chronic CAR activation led to down-regulation of these genes and to a partial loss of glutamine synthetase (GS)-positive hepatocytes. These results thus show that while chronic CAR activation per se induces HCCs carrying β-catenin mutations, it concurrently down-regulates the Wnt/β-catenin pathway in non-tumoral liver. They also indicate that the relationship between CAR and β-catenin may be profoundly different between normal and neoplastic hepatocytes.
2018-04-27 | GSE113708 | GEO