Gene expression profiles of human hepatocellular carcinoma (training set 1)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE45267 | GEO | 2014/07/31
SECONDARY ACCESSION(S): PRJNA193344
REPOSITORIES: GEO
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Project description:Hepatocellular carcinoma (HCC) in young subjects is rare but more devastating. We hypothesize that genes and etiological pathways are unique to young HCC (yHCC; ≤40 years old at diagnosis) patients. We therefore compared the gene expression profiles between yHCCs and HCCs from elderly patients.
2014-07-31 | GSE45434 | GEO
Project description:Hepatocellular carcinoma (HCC) in young subjects is rare but more devastating. We hypothesize that genes and etiological pathways are unique to young HCC (yHCC; ≤40 years old at diagnosis) patients. We therefore compared the gene expression profiles between yHCCs and HCCs from elderly patients.
2014-07-31 | GSE45435 | GEO
Project description:Hepatocellular carcinoma (HCC) is a deadly disease, often unnoticed till the late stages, where treatment options become limited. Thus, there is a critical need to identify early biomarkers for detection of the developing HCC, as well as molecular pathways that would be amenable to therapeutic intervention. While efforts using human serum and tissues from late stage patients have been undertaken, progress has been limited. We have therefore explored the possibility of utilizing established mouse models for the discovery of biomarkers, as well as to understand in a systematic manner the molecular pathways that are progressively deregulated by the various etiological factors in contributing to HCC formation. As an initial effort, we have used the Hepatitis B surface antigen (HBsAg) transgenic mice as a hepatitis model, which have been exposed to aflatoxin B1 (AFB1). In this report, we present the initial findings from a extensive longitudinal study, which confirms the synergistic effect of both these etiological factors, with a gender bias towards male mice. Tumors from the mouse models were validated both histologically as well as by molecular transcriptome analysis by comparison with human HCCs. In addition, using these models, we have identified carnitine as a novel biomarker for HCC development, which was again validated using human HCC samples. Conclusion: This study therefore highlights the utility of these mouse models in identifying biomarkers for detection of human HCCs, as well as for the systematic analysis of molecular pathways that are affected by various etiological agents during the progression of HCC from an untransformed hepatocyte, which could provide novel options for targeted therapy. liver obtained from Mus musculus which was intraperitoneally injected with AFB/oil at Day 7 and sacrificed at 15 month age. We intend to compare molecular transcriptome analysis of mouse HCC with human HCCs.
2014-01-15 | E-GEOD-54054 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) is a deadly disease, often unnoticed till the late stages, where treatment options become limited. Thus, there is a critical need to identify early biomarkers for detection of the developing HCC, as well as molecular pathways that would be amenable to therapeutic intervention. While efforts using human serum and tissues from late stage patients have been undertaken, progress has been limited. We have therefore explored the possibility of utilizing established mouse models for the discovery of biomarkers, as well as to understand in a systematic manner the molecular pathways that are progressively deregulated by the various etiological factors in contributing to HCC formation. As an initial effort, we have used the Hepatitis B surface antigen (HBsAg) transgenic mice as a hepatitis model, which have been exposed to aflatoxin B1 (AFB1). In this report, we present the initial findings from a extensive longitudinal study, which confirms the synergistic effect of both these etiological factors, with a gender bias towards male mice. Tumors from the mouse models were validated both histologically as well as by molecular transcriptome analysis by comparison with human HCCs. In addition, using these models, we have identified carnitine as a novel biomarker for HCC development, which was again validated using human HCC samples. Conclusion: This study therefore highlights the utility of these mouse models in identifying biomarkers for detection of human HCCs, as well as for the systematic analysis of molecular pathways that are affected by various etiological agents during the progression of HCC from an untransformed hepatocyte, which could provide novel options for targeted therapy.
2014-01-15 | GSE54054 | GEO
Project description:Hepatocellular carcinoma (HCC) is a deadly cancer lacking efficacious therapies. Latest studies show that cellular senescence and inflammation play key roles in HCC development, likely reflecting its etiological nature of chronic infection. A better understanding of these intertwined processes would facilitate development of therapies for malignant HCCs. Here, we show that malignant HCCs are drastically reduced after deletion of Survivin, an inhibitor of apoptosis protein. Survivin deficiency induces mitosis defect-caused metabolism reprogram and senescence in HCC cells. Survivin additionally protects both senescent and neighboring non-senescent cancer cells from cell death triggered by senescence-associated inflammatory factor TNFα. Importantly, combination of mitosis inhibitor and pro-apoptosis drug, but not alone, synergistically eliminates HCCs, recapitulating the therapeutic effect of genetic deletion of Survivin. By uncovering the role of Survivin in controlling the interaction of senescence and inflammation responses, our findings propose a strategy for HCC therapy by inducing senescence and boosting TNFα-mediated cell death.
2016-06-22 | GSE64804 | GEO
Project description:Kinetic model of GSHnet of different HCC etiological conditions.
2019-08-07 | MODEL1808060001 | BioModels
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. 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.
2010-05-18 | E-GEOD-10140 | 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. 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.
2010-05-19 | E-GEOD-10141 | biostudies-arrayexpress
Project description:Endocytosis is a cellular function which is likely to take part in HCC development due to its important role in regulating the abundances of vital signaling receptors. In this study, we aimed to investigate the expression of endocytosis-associated proteins in HCCs with various differentiation grades. Therefore, we analyzed 36 tissue specimens from HCC patients via label-free LC-MS/MS including 19 HCC tissue samples with different degrees of histological grades and 17 corresponding non-tumorous tissue controls. Following label-free analysis the abundances of SCAMP3 and CLTC were immunohistochemically examined in tissue sections of 84 HCC patients. We demonstrate the novel association of several endocytosis-associated proteins, in particular SCAMP3 with HCC progression.
2016-09-27 | PXD003552 | Pride
Project description:Chronic infections by hepatitis B virus (HBV) and hepatitis C virus (HCV) appear to be the most significant causes of hepatocellular carcinoma (HCC). Aberrant promoter methylation is known to be deeply involved in cancer, including HCC. In this study, we analyzed aberrant promoter methylation on genome-wide scale in 6 HCCs including 3 HBV-related and 3 HCV-related HCCs, 6 matched noncancerous liver tissues and 3 normal liver tissues by methylated DNA immunoprecipitation-on-chip analysis. Candidate genes with promoter methylation were detected more frequently in HCV-related HCC. Candidate genes methylated preferentially to HBV-related or HCV-related HCCs were detected and selected, and methylation levels of the selected genes were validated using 125 liver tissue samples, including 61 HCCs (28 HBV-related HCCs and 33 HCV-related HCCs) and matched 59 matched noncancerous livers, and 5 normal livers, by quantitative methylation analysis using MALDI-TOF mass spectrometry. Among analyzed genes, preferential methylation in HBV-related HCC was validated in 1 gene only. However, 15 genes were found methylated preferentially in HCV-related HCC, which was independent from age. Hierarchical clustering of HCC using these 15 genes stratified HCV-related HCC as a cluster of frequently methylated samples. The 15 genes included genes inhibitory to cancer-related signaling such as RAS/RAF/ERK and Wnt/b-catenin pathways. It was indicated that genes methylated preferentially in HCV-related HCC exist, and it was suggested that DNA methylation might play an important role in HCV-related HCC by silencing cancer-related pathway inhibitors. we analyzed aberrant promoter methylation in 6 HCC clinical samples (including 3 HBV-related HCCs and 3 HCV-related HCCs) and their matched noncancerous tissues on genome-wide scale by the method. Candidate regions of promoter methylation preferentially to HBV-related HCC and HCV-related HCC were selected, and the methylation levels of these genes were measured quantitatively using MALDI-TOF mass spectrometry. Expression levels of these 6 pairs of HCC and 4 more pairs of HCCs and surrounding noncancerous tissues were analyzed by expression array and are reported in this Series. <br><br>This experiment was reloaded in November 2010 after additional curation. this dataset is part of the TransQST collection.
2010-07-06 | E-GEOD-19665 | biostudies-arrayexpress