FABP4 overexpressed in intratumoral hepatic stellate cells within hepatocellular carcinoma with metabolic risk factors
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PROVIDER: PRJNA396548 | ENA |
REPOSITORIES: ENA
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Project description:BACKGROUND & AIMS: Metabolic syndrome is a newly identified risk factor for hepatocellular carcinoma (HCC), however the molecular mechanisms still remain unclear. To elucidate this issue, cross-species analysis was performed to compare gene expression patterns of HCC from human patients and melanocortin 4 receptor-knockout (MC4R-KO) mice, developing HCC with obesity, insulin resistance and dyslipidemia. METHODS: Unsupervised hierarchical clustering and principle component analysis of 746 differentially expressed orthologous genes classified HCC of 152 human patients and MC4R-KO mice into two distinct subgroups, one of which included all the mouse HCC was etiologically associated with metabolic risk factors, such as obesity and diabetes. A specific biomarker was identified by the integrative analysis, and validated with in vitro studies and other cohort patients. RESULTS: As commonly overexpressed in human and mouse metabolic disease-associated HCC, FABP4 was remarkably enriched in intratumoral activated hepatic stellate cells (HSCs). Then, we established subclones constitutively expressing FABP4 from a human HSC cell line, in which the expression levels of inflammatory chemokines including IL1A and IL6 was upregulated through NF-κB nuclear translocation. An immunohistochemical validation study of other 106 human HCC samples indicated that FABP4-positive HSCs were distributed in tumors of 38 cases, and that the FABP4-high group was composed of patients with non-viral and non-alcoholic HCC (P=0.027) and with multiple metabolic risk factors (P<0.001) compared with the FABP4-low. CONCLUSIONS: FABP4 overexpression in HSCs could contribute to hepatocellular carcinogenesis in patients with metabolic risk factors via modulation of inflammatory pathway, and is a promising novel biomarker as well as a potential therapeutic target for this subtype of HCC.
2018-01-28 | GSE102081 | GEO
Project description:BACKGROUND & AIMS: Metabolic syndrome is a newly identified risk factor for hepatocellular carcinoma (HCC), however the molecular mechanisms still remain unclear. To elucidate this issue, cross-species analysis was performed to compare gene expression patterns of HCC from human patients and melanocortin 4 receptor-knockout (MC4R-KO) mice, developing HCC with obesity, insulin resistance and dyslipidemia. METHODS: Unsupervised hierarchical clustering and principle component analysis of 746 differentially expressed orthologous genes classified HCC of 152 human patients and MC4R-KO mice into two distinct subgroups, one of which included all the mouse HCC was etiologically associated with metabolic risk factors, such as obesity and diabetes. A specific biomarker was identified by the integrative analysis, and validated with in vitro studies and other cohort patients. RESULTS: As commonly overexpressed in human and mouse metabolic disease-associated HCC, FABP4 was remarkably enriched in intratumoral activated hepatic stellate cells (HSCs). Then, we established subclones constitutively expressing FABP4 from a human HSC cell line, in which the expression levels of inflammatory chemokines including IL1A and IL6 was upregulated through NF-κB nuclear translocation. An immunohistochemical validation study of other 106 human HCC samples indicated that FABP4-positive HSCs were distributed in tumors of 38 cases, and that the FABP4-high group was composed of patients with non-viral and non-alcoholic HCC (P=0.027) and with multiple metabolic risk factors (P<0.001) compared with the FABP4-low. CONCLUSIONS: FABP4 overexpression in HSCs could contribute to hepatocellular carcinogenesis in patients with metabolic risk factors via modulation of inflammatory pathway, and is a promising novel biomarker as well as a potential therapeutic target for this subtype of HCC.
2018-01-28 | GSE102080 | GEO
Project description:BACKGROUND & AIMS: Metabolic syndrome is a newly identified risk factor for hepatocellular carcinoma (HCC), however the molecular mechanisms still remain unclear. To elucidate this issue, cross-species analysis was performed to compare gene expression patterns of HCC from human patients and melanocortin 4 receptor-knockout (MC4R-KO) mice, developing HCC with obesity, insulin resistance and dyslipidemia. METHODS: Unsupervised hierarchical clustering and principle component analysis of 746 differentially expressed orthologous genes classified HCC of 152 human patients and MC4R-KO mice into two distinct subgroups, one of which included all the mouse HCC was etiologically associated with metabolic risk factors, such as obesity and diabetes. A specific biomarker was identified by the integrative analysis, and validated with in vitro studies and other cohort patients. RESULTS: As commonly overexpressed in human and mouse metabolic disease-associated HCC, FABP4 was remarkably enriched in intratumoral activated hepatic stellate cells (HSCs). Then, we established subclones constitutively expressing FABP4 from a human HSC cell line, in which the expression levels of inflammatory chemokines including IL1A and IL6 was upregulated through NF-κB nuclear translocation. An immunohistochemical validation study of other 106 human HCC samples indicated that FABP4-positive HSCs were distributed in tumors of 38 cases, and that the FABP4-high group was composed of patients with non-viral and non-alcoholic HCC (P=0.027) and with multiple metabolic risk factors (P<0.001) compared with the FABP4-low. CONCLUSIONS: FABP4 overexpression in HSCs could contribute to hepatocellular carcinogenesis in patients with metabolic risk factors via modulation of inflammatory pathway, and is a promising novel biomarker as well as a potential therapeutic target for this subtype of HCC.
2018-01-28 | GSE102079 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-01-27 | GSE102083 | GEO
Project description:FABP4 overexpressed in intratumoral hepatic stellate cells within hepatocellular carcinoma with metabolic risk factors (part 2)
| PRJNA396557 | ENA
Project description:FABP4 overexpressed in intratumoral hepatic stellate cells within hepatocellular carcinoma with metabolic risk factors (part 3)
| PRJNA396556 | ENA
Project description:FABP4 overexpressed in intratumoral hepatic stellate cells within hepatocellular carcinoma with metabolic risk factors (part 1)
| PRJNA396559 | ENA
Project description:Fatty acid-binding protein 4 (FABP4) plays an essential role in metabolism and inflammatory. However, the role of FABP4 in alcoholic steatohepatitis (ASH) remains unclear. This study aimed to investigate the function of FABP4 and the underlying mechanisms in the progression of ASH.
2024-04-24 | GSE265758 | GEO
Project description:We identified the genomic characteristics of peritumoral hepatic stellate cells (HSCs) in HBV related HCC. Expression levels of 17160 genes were compared between quiescent and activated HSCs and cancer associated myofibroblasts (CAMFs) from three independent samples per group. We find that among all significant changed genes (≥2-fold change and p<0.05), there were only 188 upregulated and 467 downregulated genes in peritumoral HSCs compared to intratumoral CAMFs. Compared with quiescent HSCs, the same patients-derived culture activated HSCs yielded as many as 1485 upregulated and 1471 downregulated genes. Between peritumoral HSCs/intratumoral CAMFs and culture-activated HSCs , there are 4479 and 3540 upregulated genes, and 3691 and 3380 downregulated genes, respectively. Between peritumoral HSCs/intratumoral CAMFs and quiescent phenotype HSCs, there are 1032 and 994 upregulated genes, and 1654 and 1188 downregulated genes, respectively.
2019-01-03 | GSE124552 | GEO
Project description:FABP4 has been reported to trigger ADAMTS4 overexpression in chondrocytes. Here we described the transcriptional changes of FABP4-treatment.
2023-06-22 | GSE227483 | GEO