Wolf_et_al
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Kristian Unger
PROVIDER: E-MTAB-2469 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Genomic copy number profiling of hepatocellular carcinomas (HCC) from IKKβ(EE)Hep mice (C57BL/6) constitutively expressing IKKβ in the liver without and after treatment with DEN (diethylnitrosamine) and of HCCs that developed in wild type mice (C57BL/6) after DEN treatment.
2015-09-25 | E-MTAB-3848 | biostudies-arrayexpress
Project description:Comparison of the genomic copy number status of livers from wildtype mice (reference) with Tak1/Casp8 knockout mice or Tak1/LPC knockout mice or Tak1/LPC/RIP3 knockout mice.
2013-07-22 | E-MTAB-1559 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) is a highly heterogeneous disease, and prior attempts to develop genomic-based classification for HCC have yielded highly divergent results, indicating difficulty in identifying unified molecular anatomy. We performed a meta-analysis of gene expression profiles in data sets from eight independent patient cohorts across the world. In addition, aiming to establish the real world applicability of a classification system, we profiled 118 formalin-fixed, paraffin-embedded tissues from an additional patient cohort. A total of 603 patients were analyzed, representing the major etiologies of HCC (hepatitis B and C) collected from Western and Eastern countries. We observed three robust HCC subclasses (termed S1, S2, and S3), each correlated with clinical parameters such as tumor size, extent of cellular differentiation, and serum alpha-fetoprotein levels. An analysis of the components of the signatures indicated that S1 reflected aberrant activation of the WNT signaling pathway, S2 was characterized by proliferation as well as MYC and AKT activation, and S3 was associated with hepatocyte differentiation. Functional studies indicated that the WNT pathway activation signature characteristic of S1 tumors was not simply the result of beta-catenin mutation but rather was the result of transforming growth factor-beta activation, thus representing a new mechanism of WNT pathway activation in HCC. These experiments establish the first consensus classification framework for HCC based on gene expression profiles and highlight the power of integrating multiple data sets to define a robust molecular taxonomy of the disease. Surgically resected 118 tumor tissues from patients with hepatocellular carcinoma (HCC)
2009-09-08 | E-GEOD-10186 | biostudies-arrayexpress
Project description:Breast cancer is a heterogeneous disease classified into 3 major subtypes based on the presence or absence of molecular markers for oestrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor-2 (Her2) . Hormone receptor-positive BC (ER+, PR+ and Her-2-), accounts for approximately 70% of patients. Patients with ER- BC account for approximately 30 % of all cases and commonly have a worse prognosis than ER+ patients (9). However, a significant proportion of ER- cases have good outcomes and could potentially benefit from a less aggressive therapy. Triple negative breast cancer (TNBC, ER-, PR- and Her-2-) accounts for approximately 15% of breast cancers and has the poorest outcomes. An hypoxic microenvironment is an important intrinsic component of solid tumours that can result in rapid proliferation of cancer cells and is associated with the lack of oxgyen and abnormal tumour blood vessels. Hypoxia stimulates the hypoxia inducible factor-1α (HIF-1α) that transactivates genes associated with angiogenesis, tumour growth, metastasis, metabolic reprogramming, and treatment resistance. HIF-1α is recognised to induce the expression of carbonic anhydrase IX (CAIX), an enzyme that has been attributed a central role in pH regulation and cancer progression and is particularly pronounced in peri necrotic tumour areas, high-grade BCs. The adaption to hypoxia is governed by multiple transcriptional and post-transcriptional changes in gene expression. Up to 1.5 % of the human genome is estimated to be transcriptionally responsive to hypoxia. Genes and pathways which have been identified as being responsive to hypoxia may have the potential to be used as prognostic or predictive markers, and furthermore, can help identify novel therapeutic targets. The aim of the present study was to gain a better understanding of the transcriptomic and protein pathways associated with CAIX in ER- BC to identify potential therapeutic targets against this aggressive phenotype.
2023-07-31 | E-MTAB-11955 | biostudies-arrayexpress
Project description:In this study, we show that intratumoral injections of the trivalent measles, mumps, and rubella (MMR) live attenuated viral vaccine (LAVs) modulate a potent cytotoxic T cells immune response, resulting in tumor growth inhibition and improved survival in syngeneic mouse models of hepatocellular carcinoma (HCC) and colorectal cancer (CRC).
2022-10-27 | PXD031295 | Pride
Project description:Background: Hepatocellular carcinoma (HCC) is among the top-five cancer killers worldwide. Here, we describe our analysis of 20 gene signatures with reported prognostic value in a cohort of patients with early stage HCC treated with surgical resection. Methods: We performed gene-expression profiling of 164 formalin-fixed, paraffin-embedded HCC from three hepatology centers participating the HCC Genomic Consortium. We utilized IlluminaM-bM-^@M-^Ys whole-genome DASL assay measuring ~24,000 annotated human genes. We evaluated genomic concordance and prognostic performance of 20 already reported prognostic gene signatures. Additionally, since only the largest nodule was profiled, we also excluded patients with multiple tumors to avoid biases related to intra-individual genomic tumor heterogeneity. Results: Among the 20 signatures evaluated, 15 were able to confidently allocate patients (FDR<0.05) within their predicted poor-outcome subclass. Pairwise comparisons showed a significant overlap between almost all poor-outcome signatures derived from the tumor (P<0.001), except for the metastatic HCC signature. Interestingly, poor-outcome signatures from the tumor were not significantly associated with those obtained from non-tumor adjacent tissue in the same patient. The prognosis analysis for earliest stages (BCLC 0 or A) with single nodules revealed that the G3 signature reported by Boyault et al. Conclusions: We present a composite genomic model for prediction of tumor recurrence in early HCC. It will allow risk stratification, personalized surveillance, and eventually customized interventions in patients with early HCC candidates for resection. Samples with "used for prognostic prediction: yes" were included in the study. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2011-02-17 | E-GEOD-20140 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC), which accounts for 90% of all primary livers tumors, is the fourth most common cancer in the world. The development of HCC is a long-term and complex process, and uncovering the molecular mechanisms associated with HCC development is critical for the disease diagnosis, prevention, and treatment. Exploring these mechanisms using human HCC samples is desirable, but frequently impractical, with a number of limitations and shortcomings. The STAMTM (Stelic Institute & Co, Tokyo, Japan) mouse model of NASH-associated liver carcinogenesis is considered a useful and relevant model for investigating the molecular pathogenesis of NASH-derived HCC. This model resembles the human HCC development associated with progression from simple steatosis to NASH, fibrosis, and HCC. In the present study, by using high-throughput whole genome microarrays (SurePrint G3 Mouse Gene Expression v2, 8x60K; Agilent Technologies, Santa Clara, CA), we examined the transcriptomic profiles in the livers of STAMTM mice at different stages of liver carcinogenesis, including steatosis (6 week time interval), NASH (8 weeks), fibrotic stage (12 weeks), and in full-fledged HCC (20 weeks). The results of microarray analyses showed significant progressive changes in hepatic gene expression during the development of HCC. A total of 970, 1462, 2742, and 2857 of differentially expressed genes were identified in the livers at 6, 8, 12, and 20 weeks, respectively. Detailed analysis of these differentially expressed genes will benefit the understanding of the underlying mechanisms of non-alcoholic fatty liver disease-derived HCC. Transcriptomic profile in the liver of STAM mice at 6 weeks (steatosis; n=3), 8 weeks (steatohepatitis; n=3) 12 weeks (fibrosis; n=4) and 20 weeks (HCC-stage tumor tissue, n=4) weeks. Age-matched control samples were also analyzed.
2016-06-22 | E-GEOD-83596 | biostudies-arrayexpress
Project description:Purpose: Preclinical model systems should faithfully reflect the complexity of the human pathology. In hepatocellular carcinoma (HCC), the tumor vasculature is of particular interest in diagnosis and therapy. By comparing two commonly applied preclinical model systems, diethylnitrosamine induced (DEN) and orthotopically implanted (McA) rat HCC, we aimed to measure tumor biology non-invasively and identify differences between the models.<br>Experimental design: DEN and McA tumor development was monitored by magnetic resonance imaging (MRI) and positron emission tomography (PET). A slice-based correlation of imaging and histopathology was performed. Array CGH analyses were applied to determine genetic heterogeneity. Therapy response to sorafenib was tested in DEN and McA tumors.<br>Results: Histologically and biochemically confirmed liver damage resulted in increased 18F-fluordeoxyglucose (FDG) PET uptake and perfusion in DEN animals only. DEN tumors exhibited G1-3 grading compared to uniform G3 grading of McA tumors. Array comparative genomic hybridization revealed a highly variable chromosomal aberration pattern in DEN tumors. Heterogeneity of DEN tumors was reflected in more variable imaging parameter values. DEN tumors exhibited lower mean growth rates and FDG uptake and higher diffusion and perfusion values compared to McA tumors. To test the significance of these differences, the multikinase inhibitor sorafenib was administered, resulting in reduced volume growth kinetics and perfusion in the DEN group only.<br>Conclusion: This work depicts the feasibility and importance of in depth preclinical tumor model characterization and suggests the DEN model as a promising model system of multifocal nodular HCC in future therapy studies.
2016-03-25 | E-MTAB-3507 | biostudies-arrayexpress
Project description:Genetic variations play an important role in tumor development and metastasis. Hepatocellular carcinoma (HCC) is one of leading cause of cancer-related death. Despite improvements in surveillance and clinical treatment strategies, the prognosis of HCC remains dismal. Affymetrix SNP 6.0 array were used to evaluate the genetic characteristics of tumor DNA in 30 HBV-related HCC patients who were underwent liver transplantation. Recurrence related SNPs were selected and validated. Affymetrix SNP 6.0 arrays were performed according to the manufacturer's directions on DNA extracted from formalin-fixed paraffin-embedded HCC tissues
2012-10-26 | E-GEOD-29667 | biostudies-arrayexpress
Project description:Background: It is a challenge to identify those patients who, after undergoing potentially curative treatments for hepatocellular carcinoma, are at greatest risk of recurrence. Such high-risk patients could receive novel interventional measures. An obstacle to the development of genome-based predictors of outcome in patients with hepatocellular carcinoma has been the lack of a means to carry out genomewide expression profiling of fixed, as opposed to frozen, tissues. Methods: We aimed to demonstrate the feasibility of gene-expression profiling of more than 6000 human genes in formalin-fixed paraffin-embedded tissues. We applied the method to tissues from 307 patients with hepatocellular carcinoma, from four series of patients, to discover and validate a gene-expression signature associated with survival. Results: The expression-profiling method for formalin-fixed, paraffin-embedded tissue was highly effective: samples from 90% of the patients yielded data of high quality, including samples that had been archived for more than 24 years. Gene-expression profiles of tumor tissue failed to yield a significant association with survival. In contrast, profiles of the surrounding nontumoral liver tissue were highly correlated with survival in a training set of 82 Japanese patients, and the signature was validated in tissues from an independent group of 225 patients from the United States and Europe (p = 0.04). Conclusions: We have demonstrated the feasibility of genomewide expression profiling of formalin-fixed, paraffin-embedded tissues and have shown that a reproducible gene-expression signature correlating with survival is present in liver tissue adjacent to the tumor in patients with hepatocellular carcinoma. This SuperSeries is composed of the following subset Series: GSE10140: Gene Expression in Fixed Tissues and Outcome in Hepatocellular Carcinoma (Training Set, Liver) GSE10141: Gene Expression in Fixed Tissues and Outcome in Hepatocellular Carcinoma (Training Set, HCC) GSE10142: Gene Expression in Fixed Tissues and Outcome in Hepatocellular Carcinoma (Validation Set) Keywords: Hepatocellular carcinoma, Expression array, Illumina, Signatures, Outcome prediction Training cohort: 80 tumor and 82 non-tumor liver tissues surgically resected from patients with hepatocellular carcinoma (HCC); Validation cohort: 225 non-tumor liver tissues surgically resected from patients with HCC. Clinical data has been withheld from GEO due to privacy concerns.
2010-05-20 | E-GEOD-10143 | biostudies-arrayexpress