Gene expression profiles of 75 tissue samples were analyzed representing the stepwise carcinogenic process from pre-neoplastic lesions (cirrhosis and dysplasia) to HCC, including four neoplastic stages (very early HCC to metastatic tumors) from patients with HCV infection. Gene signatures that accurately reflect the pathological progression of disease at each stage were identified and potential molecular markers for early diagnosis uncovered. Pathway analysis revealed dysregulation of the Notch and Toll-like receptor pathways in cirrhosis, followed by deregulation of several components of the Jak/STAT pathway in early carcinogenesis, then up-regulation of genes involved in DNA replication and repair and cell cycle in late cancerous stages.
Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene-expression signature of vascular invasion in hepatocellular carcinoma.
Sex, Age, Specimen part
View SamplesHepatocellular carcinoma (HCC) is a complex and heterogeneous tumor due to activation of multiple cellular pathways and molecular alterations. Herein, we report the first molecular classification of 89 HCC based on the expression of 358 microRNAs and integrative genomic analysis. Three main subclasses of HCC were identified : two of them were associated with beta-catenin mutations or aggressive phenotype. A subset of the subclass of aggressive tumors (8/89, 9%) showed overexpression of a cluster of microRNAs located on chr19q13.41 (C19MC locus. We showed that miR 517a, representing C19MC, promoted cell proliferation, migration and invasion in vitro and induced the development of aggressive tumors in vivo suggesting its role as a novel oncogenic driver in HCC.
MicroRNA-based classification of hepatocellular carcinoma and oncogenic role of miR-517a.
Sex, Age, Specimen part
View SamplesmRNA expression profile modified by stable transfection of microRNA mir-517a (MIR517A) in a human hepatocellular carcinoma cell line Huh-7
MicroRNA-based classification of hepatocellular carcinoma and oncogenic role of miR-517a.
No sample metadata fields
View SamplesAffymetrix soybean genome arrays were used to identify genes differentially expressed in the immune resistance response at 6, 12, 24, and 48 hours after inoculation with Phakopsora pachyrhizi isolates TW72-1 or HW94-1
A microarray analysis for differential gene expression in the soybean genome using Bioconductor and R.
No sample metadata fields
View SamplesThe data are derived from anonymized patient samples for which demographic information is not provided
Focal gains of VEGFA and molecular classification of hepatocellular carcinoma.
Sex, Age
View SamplesTo 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.
Focal gains of VEGFA and molecular classification of hepatocellular carcinoma.
Sex, Age
View SamplesBackground: Cystic fibrosis (CF) is caused by mutations in the CFTR gene that impair function of this cAMP-regulated Cl- channel. In the small intestine, loss of CFTR function creates a dehydrated, acidic luminal environment which is believed to cause an accumulation of mucus, a phenotype characteristic of CF. CF mice have an innate immune response and impaired intestinal transit as well. We investigated whether lubiprostone, which activates the CLC2 Cl- channel, would improve the CF intestinal phenotype.
Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype.
Specimen part, Treatment
View SamplesA phylogenetic analysis of seven different species (human, mouse, rat, worm, fly, yeast, and plant) utilizing all (541) basic helix-loop-helix (bHLH) genes identified, including expressed sequence tags (EST), was performed. A super-tree involving six clades and a structural categorization involving the entire coding sequence was established. A nomenclature was developed based on clade distribution to discuss the functional and ancestral relationships of all the genes. The position/location of specific genes on the phylogenetic tree in relation to known bHLH factors allows for predictions of the potential functions of uncharacterized bHLH factors, including EST's. A genomic analysis using microarrays for four different mouse cell types (i.e. Sertoli, Schwann, thymic, and muscle) was performed and considered all known bHLH family members on the microarray for comparison. Cell-specific groups of bHLH genes helped clarify those bHLH genes potentially involved in cell specific differentiation. This phylogenetic and genomic analysis of the bHLH gene family has revealed unique aspects of the evolution and functional relationships of the different genes in the bHLH gene family. PMID: 18557763
Phylogenetic and expression analysis of the basic helix-loop-helix transcription factor gene family: genomic approach to cellular differentiation.
Sex, Specimen part
View SamplesPurpose: To identify novel genes regulated by the aryl hydrocarbon receptor that influence human Th17 cell function. Methods: Naïve CD4 T cells from peripheral blood of six healthy human volunteers were cultured under four experimental conditions for three days: anti-CD3 and anti-CD28 antibodies (Media control), Media with Th17 conditions (IL-6, TGF-b, IL-1b, IL-23), Th17+FICZ and Th17+CH223191. Total RNA was extracted from each sample on day 3 and sequenced in a paired-end 2x50bp strategy on an Illumina HiSeq1500. A total of six donors were analyzed. Results: AhR activation with FICZ suppressed IL-17 production from human CD4 T cells and increased IL-22. AhR inhibition with CH223191 potently suppressed IL-22 and modestly increased IL-17 production. On day 3, the number of significantly regulated genes for each treatment were 975 (Th17), 88 (Th17+FICZ) and 142 (Th17+CH223191). 11 common genes were significantly regulated by all three treatments. One of these, GPR68, was investigated further in functional studies since its expression correlated with IL-22 production. Activation of GPR68 with a positive allosteric modulator suppressed IL-22 concentrations in human Th17 cell cultures. Conclusions: Our study demonstrates that GPR68 activation can negatively regulate IL-22 production from human CD4 T cells in the presence of an AhR agonist. RNA-seq is a powerful method to identify novel gene targets that regulate cytokines involved in chronic inflammatory diseases. Overall design: Naïve CD4 T cells were purified from peripheral blood mononuclear cells isolated from six patient samples. Four experimental conditions were created for each sample: media only (control); Th17 differentiated; Th17+FICZ; and Th17+CH223191. Total RNA was extracted from each sample on day 3 and sequenced in a paired-end 2x50bp strategy on an Illumina HiSeq1500. Differential gene expression analysis identified genes that were expressed at significantly different levels than the control (Media). Ingenuity pathway analysis revealed the most common cellular functions for genes regulated by each treatment.
Cytokine Regulation in Human CD4 T Cells by the Aryl Hydrocarbon Receptor and Gq-Coupled Receptors.
Specimen part, Treatment, Subject
View Samples