Evaluation of ATAD2 as a potential target in hepatocellular carcinoma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA737831 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We evaluated differentially expressed genes (DEGs) between hepatocellular carcinoma cell lines (Hep3B, SNU449, and PLC/PRF/5) treated with ATAD2 siRNA or control using Affymetrix array data whether ATAD2 could be potential target in hepatocellular carcinoma.
2022-06-15 | GSE178243 | GEO
Project description:Custom gene expression panel for evaluation of potential molecular markers in hepatocellular carcinoma
| PRJNA790925 | ENA
Project description:We studied 20 candidate genes (HCC hub genes, potential drug target genes, predominant somatic mutant genes) retrieved from available literature and public databases with potential to be used as biomarkers for the prognosis of HCC and prediction of treatment outcome. We analysed expression of the genes by RT-qPCR in 30 HCC tumor and adjacent non-tumor paired samples from Vietnamese patients.
2021-12-25 | GSE191298 | GEO
Project description:Epigenetic deregulation is a critical event in human malignancies. A number of DNA methylation markers are currently under evaluation as diagnostic and prognostic biomarkers for many cancers. However, its potential role in hepatocellular carcinoma (HCC) is under-explored. Aims: To develop a DNA methylation-based prognostic signature in surgically resected HCC
2015-02-13 | GSE56588 | GEO
Project description:Cancer-associated Fibroblast-derived SPP1 is a Potential Target for Overcoming Sorafenib and Lenvatinib Resistance in Hepatocellular Carcinoma
| PRJNA793786 | ENA
Project description:A comprehensive screening of glycopeptides as candidate biomarkers from human serum for early diagnosis of NASH hepatocellular carcinoma using a stepped HCD method and PRM evaluation. Glycopeptides from vitronectin(VTNC) has been reported as biomarkers for NASH-related HCCs.
2021-05-10 | PXD025455 | Pride
Project description:Abstract: Cancer-associated fibroblasts (CAFs) play an important role in the induction of chemo-resistance. The objectives of this study were to clarify the mechanism underlying CAF-mediated sorafenib/lenvatinib resistance and identify a novel therapeutic target to overcome resistance to sorafenib/lenvatinib in hepatocellular carcinoma (HCC). Methods: Whole transcriptome sequencing (WTS) data of nine pairs of CAFs and para-cancer-associated fibroblasts (PAFs) were analyzed to identify key molecules that induce resistance to tyrosine kinase inhibitors (TKIs). In vitro and in vivo experiments were performed to validate selected targets and related mechanisms. Plasma secreted phosphoprotein 1 (SPP1) expression levels prior to sorafenib/lenvatinib treatment as well as progression-free survival (PFS) and overall survival (OS) of an advanced HCC cohort (n=42) were evaluated using Kaplan–Meier analysis. Results: Co-culturing CAFs and HCC cells significantly reduced the responsiveness of HCC cells to sorafenib/lenvatinib, in vitro and in vivo. Systematic integrative analysis of the WTS data of CAFs/PAFs and publicly available gene expression data indicated that CAF-derived SPP1 (CAF-SPP1) was suitable for use as a candidate molecule to induce sorafenib/lenvatinib resistance. An evaluation of the mechanisms involved indicated that CAF-SPP1 increased phosphorylation of PKCɑ, which then activated rapidly accelerated fibrosarcoma (RAF)-extracellular signal-related kinase 1/2-signal transducer and activator of transcription 3 (STAT3) and phosophoinositide 3-kinase (PI3K)-AKT-mechanistic target of rapamycin kinase (mTOR) in HCC cells. SPP1 inhibitors reversed CAF-induced sorafenib/lenvatinib resistance in vitro and in vivo. Patients showing high plasma SPP1 prior to sorafenib/lenvatinib treatment exhibited significantly poor PFS (P=0.005) and OS (P=0.041). Conclusions: CAF-SPP1 enhances sorafenib/lenvatinib resistance in HCC by alternatively activating oncogenic pathways via PKCɑ phosphorylation. Inhibition of CAF-SPP1 may be utilized as a therapeutic strategy against TKI resistance in HCC. Plasma SPP1 level prior to TKI treatment shows potential as a promising biomarker for predicting sorafenib/lenvatinib response in advanced HCC patients.
2022-12-24 | GSE192912 | GEO
Project description:The placental growth factor (PlGF) is member of the vascular endothelial growth factor (VEGF)-family known to stimulate endothelial cell growth, migration and survival, attract angiocompetent macrophages and bone marrow progenitor cells and determine the metastatic niche. Unlike VEGF, genetic studies have shown that PlGF is specifically involved in the pathologic angiogenesis, thus its inhibition would not affect healthy blood vessels, providing an attractive drug candidate with a good safety profile. In this study, we assess whether inhibition of PlGF could be used as a potential therapy against hepatocellular carcinoma (HCC), by using PlGF-knock out mice and monoclonal antibodies targeting PlGF in an orthotopic model for HCC. In addition, the effect of PlGF-antibodies is compared to that of Sorafenib, as well as the combination of both therapies. In our study we have found that both in a transgenic knock out model as in a treatment model, silencing or inhibition of PlGF significantly decreased tumour burden, not only by inhibiting the vascularisation, but also by decreasing hepatic macrophage recruitment and by normalizing the remaining blood vessels, thereby decreasing hypoxia and thus, reducing the pro-metastatic potential of HCC. Conclusion: considering its favourable safety profile and its pleiotropic effect on vascularisation, metastasis and inflammation, targeting PlGF could become a valuable therapeutic strategy against HCC. Hybridisation on the Mouse Gene Expression Microarray (Agilent) was performed in a single sample per chip and in a monocolore mode, using cyanine-3 (Cy3) labeling. Following conditions were assessed: 25W DEN + 5W αPlGF tumour tissue (n = 5), 25W DEN + 5W αPlGF surrounding tissue (n = 4), 25W DEN + 5W IgG tumour tissue (n = 5), 25W DEN + 5W IgG surrounding tissue (n = 4), 25W saline + 5W αPlGF (n = 3) and 25W saline + 5W IgG (n = 3).
2014-12-23 | E-GEOD-35289 | biostudies-arrayexpress
Project description:Massive studies have been applied in exploring the factors driving pathogenesis, progression and metastasis of hepatocellular carcinoma. However these studies were inefficient in disclosing the fundamental mechanism which promotes hepatocellular carcinoma. Zinc and zinc-finger proteins have been important in extensive biological processes for human. Supervised machine learning using bootstrapping algorithm on GEO and TCGA transcriptome data for hepatocellular carcinoma identified zinc-finger like protein ZFPL1 as potential hepatocellular carcinoma driver. Further studies validated ZFPL1 significantly promoted progression and metastasis of hepatocellular carcinoma. We performed RNA-seq on si-ZFPL1 xenograft tissue and identified CLDN3 as potential target gene for ZFPL1. Further experiments confirmed interaction between ZFPL1 and WNT signaling pathway markers. Conclusively, these studies indicated the effect and mechanism of ZFPL1 on promoting progression and metastasis of hepatocellular carcinoma and might gap the bridge between zinc-finger like proteins and hepatocellular carcinoma.
2024-10-19 | GSE277010 | GEO
Project description:The placental growth factor (PlGF) is member of the vascular endothelial growth factor (VEGF)-family known to stimulate endothelial cell growth, migration and survival, attract angiocompetent macrophages and bone marrow progenitor cells and determine the metastatic niche. Unlike VEGF, genetic studies have shown that PlGF is specifically involved in the pathologic angiogenesis, thus its inhibition would not affect healthy blood vessels, providing an attractive drug candidate with a good safety profile. In this study, we assess whether inhibition of PlGF could be used as a potential therapy against hepatocellular carcinoma (HCC), by using PlGF-knock out mice and monoclonal antibodies targeting PlGF in an orthotopic model for HCC. In addition, the effect of PlGF-antibodies is compared to that of Sorafenib, as well as the combination of both therapies. In our study we have found that both in a transgenic knock out model as in a treatment model, silencing or inhibition of PlGF significantly decreased tumour burden, not only by inhibiting the vascularisation, but also by decreasing hepatic macrophage recruitment and by normalizing the remaining blood vessels, thereby decreasing hypoxia and thus, reducing the pro-metastatic potential of HCC. Conclusion: considering its favourable safety profile and its pleiotropic effect on vascularisation, metastasis and inflammation, targeting PlGF could become a valuable therapeutic strategy against HCC.
2014-12-23 | GSE35289 | GEO