Re-expression of fetal IGF2 as a target for hepatocellular carcinoma therapy
Ontology highlight
ABSTRACT:
ORGANISM(S): synthetic construct Homo sapiens
PROVIDER: GSE74618 | GEO | 2016/11/03
SECONDARY ACCESSION(S): PRJNA301004
REPOSITORIES: GEO
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Project description:Hepatocellular carcinoma (HCC) affects millions of people worldwide and is a lethal malignancy for which there are no effective therapies. To identify prognostic gene markers for liver cancer, we conducted transcriptome profiling of frozen tissues (tumor and non-tumor) from 300 early-to-advanced stage HCCs plus 40 cirrhotic and 6 normal livers. We have profiles 268 HCC tumor, 243 adjacent non-tumor, 40 cirrhotic and 6 healthy liver samples.
2011-07-05 | E-GEOD-25097 | biostudies-arrayexpress
Project description:A Cartes d'Identite des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net) | Affymetrix HG-U133 Plus 2.0 : 5 mixed fibrolamellar carcinoma (m-FLC), 17 pure fibrolamellar carcinoma (p-FLC), 7 hepatocelluar carcinoma arising in non-cirrhotic liver (nc-HCC) and 10 non-tumoral livers (NL).
2014-08-15 | E-MTAB-1503 | biostudies-arrayexpress
Project description:Background & Aims: Chronic liver inflammation causes continuous liver damage with progressive liver fibrosis and cirrhosis, which may eventually lead to hepatocellular carcinoma (HCC). Whereas, the ten-year incidence for HCC in cirrhotic patients is approximately 20%, many cirrhotic patients remain tumor-free for their entire lives. Therefore, we wanted to clarify the mechanisms defining the different outcomes of chronic liver inflammation. Methods: We designed a longitudinal study comparing the mRNA and miRNA expression profiles in matched non-tumoral liver tissue from patients developing HCC (n = 30) versus patients remaining tumor-free (n = 27). The liver parenchyma was analyzed before and after HCC development in the same patient. Cirrhotic patients remaining tumor-free within a similar time frame served as a control cohort. mRNA expression of genes associated with cancer development and miRNAs were examined by the nCounterNanostring technology. The role of the identified genes involved in HCC development was evaluated by immunohistochemistry and in vitro assays. Results: Comparison of the two cohorts revealed that liver tissue from patients developing HCC displayed activation of NF-B, Insulin receptor and PI3K-AKT pathways, in parallel with increased hepatocyte proliferation and damage. Furthermore, downregulation of miR-579-3p was found as an early step in HCC development. MiR-579-3p directly attenuated PIK3CA expression and consequently AKT and pAKT. In vitro analyses confirmed that miR-579-3p controlled cell proliferation, migration and colony formation. Conclusions: Liver tissues from patients developing HCC revealed a more severe damage to the parenchyma with elevated hepatocyte proliferation. Moreover, miR-579-3p was identified as a potential novel tumor suppressor regulating PI3K-AKT signalling at the early stages of HCC development.
2021-06-20 | GSE116044 | GEO
Project description:Background & Aims: Chronic liver inflammation causes continuous liver damage with progressive liver fibrosis and cirrhosis, which may eventually lead to hepatocellular carcinoma (HCC). Whereas, the ten-year incidence for HCC in cirrhotic patients is approximately 20%, many cirrhotic patients remain tumor-free for their entire lives. Therefore, we wanted to clarify the mechanisms defining the different outcomes of chronic liver inflammation. Methods: We designed a longitudinal study comparing the mRNA and miRNA expression profiles in matched non-tumoral liver tissue from patients developing HCC (n = 30) versus patients remaining tumor-free (n = 27). The liver parenchyma was analyzed before and after HCC development in the same patient. Cirrhotic patients remaining tumor-free within a similar time frame served as a control cohort. mRNA expression of genes associated with cancer development and miRNAs were examined by the nCounterNanostring technology. The role of the identified genes involved in HCC development was evaluated by immunohistochemistry and in vitro assays. Results: Comparison of the two cohorts revealed that liver tissue from patients developing HCC displayed activation of NF-B, Insulin receptor and PI3K-AKT pathways, in parallel with increased hepatocyte proliferation and damage. Furthermore, downregulation of miR-579-3p was found as an early step in HCC development. MiR-579-3p directly attenuated PIK3CA expression and consequently AKT and pAKT. In vitro analyses confirmed that miR-579-3p controlled cell proliferation, migration and colony formation. Conclusions: Liver tissues from patients developing HCC revealed a more severe damage to the parenchyma with elevated hepatocyte proliferation. Moreover, miR-579-3p was identified as a potential novel tumor suppressor regulating PI3K-AKT signalling at the early stages of HCC development.
2021-06-20 | GSE116043 | GEO
Project description:Ηepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Early de-tection/diagnosis is vital for the prognosis of HCC whereas diagnosis at late stages is associated with very low survival rate. Early diagnosis is based on patient’s 6 month surveillance and use of at least two imaging modalities. The aim of this study was to investigate diagnostic markers for the detection of early HCC based on proteome analysis, microRNAs (miRNAs) and circulat-ing tumor cells (CTCs) in the blood of patients with cirrhosis, early and advanced HCC. We studied 89 patients with HCC of whom 33 had early HCC and 28 cirrhotic patients. CTCs were detected by Real-Time Quantitative Reverse Transcription PCR and immunofluorescence using the markers Epithelial cell adhesion molecule (EPCAM), Vimentin, A Fetoprotein (AFP) and surface major Vault protein (sMVP). Expression of the five most commonly HCC-involved miRNAs (miR-122, miR-200a, miR-200b, miR-221, miR-222) was examined in the serum by qRT-PCR. Finally patient serum was analyzed by whole proteome analysis (LC/MS). Twenty seven out of 53 (51%) patients with advanced HCC had detectable CTCs. Among them, 10/27 (37%) presented evidence of mesenchymal or intermediate stage cells (vimentin and/or sMVP positive). Moreover, 5/17 (29%) patients with early HCC and 6/28 (21%) cirrhotic patients had detectable CTCs. Patients with early and advanced HCC exhibited a significant increase of miR-200b when compared to cirrhotic patients. Our proteome analysis indicated that early HCC patients present a significant upregulation of APOA2, APOC3 proteins when compared to cir-rhotic patients, that when used in combination, cover the 100% of the patients with early HCC. In conclusion, miR-200b, APOA2 and APOC3 proteins are sensitive markers and can be poten-tially useful in combination for the early diagnosis of HCC.
2023-03-11 | PXD033306 | Pride
Project description:Six frozen hepatocellular carcinoma (HCC) samples (three without cirrhotic and three with cirrhotic background) were selected to analyze the circRNA expression profile through circRNA-seq. A total of 20334 circRNAs were identified in these tumor tissues, which were widely distributed in all chromosomes. Differential analysis revealed that 393 were significantly dysregulated in non-cirrhotic HCC when compared with cirrhotic HCC tissues (log2(fold change) > 1 and p < 0.05). Our study undoubtedly provide a new insight in investigating the initiation of HCC.
2022-05-10 | GSE193862 | GEO
Project description:We profiled miRNA expression in tissue samples (104 HCC, 90 adjacent cirrhotic livers, 21 normal livers) as well as in 35 HCC cell lines. A set of 12 miRNAs (including miR-21, miR-221/222, miR-34a, miR-519a, miR-93,miR-96, and let-7c) was linked to disease progression from normal liver through cirrhosis to full-blown HCC. miR-221/222, the most upregulated miRNAs in tumor samples, are shown to target the CDK inhibitor p27 and to enhance cell growth in vitro. Conversely, these activities can be efficiently inhibited by an antagomiR specific for miR-221. In addition, we show, using a mouse model of liver cancer, that miR-221 overexpression stimulates growth of tumorigenic murine hepatic progenitor cells.
2009-12-08 | E-TABM-866 | biostudies-arrayexpress
Project description:In this study RNAseq was used for studying the transcriptome profile of primary liver sinusoidal endothelial cells (LSECs) isolated from non-lesioned non-tumorous liver tissues (considered as healthy) and from cirrhotic liver explants (ethanol etiology). Results showed different transcriptomic profile between two populations of LSECs with 1374 significant deregulated genes (fold-change>1.5 and p-vale<0.05) in cirrhotic-LSECs compared with healthy-LSECs.
2021-09-24 | GSE164799 | GEO
Project description:Hepatocellular carcinoma (HCC) is a prevalent human cancer with rising incidence worldwide. Human HCC is frequently associated with chronic liver inflammation and cirrhosis, pathophysiological processes that are a consequence of chronic viral infection, disturbances in metabolism, or exposure to chemical toxicants. To better characterize the pathogenesis of HCC, we used a human disease-relevant mouse model of fibrosis-associated hepatocarcinogenesis. In this model, marked liver tumor response caused by a pro-mutagenic chemical N-nitrosodiethylamine in presence of liver fibrosis was associated with epigenetic events indicative of genomic instability. Therefore, we hypothesized that DNA copy number alterations (CNAs), a feature of genomic instability and a common characteristic of cancer, are concordant between human HCC and mouse models of fibrosis-associated hepatocarcinogenesis. We evaluated DNA CNAs and changes in gene expression in the mouse liver (normal, tumor and non-tumor cirrhotic tissues). In addition, we compared our findings to those in human HCC (tumor and non-tumor cirrhotic/fibrotic tissues). We observed that while fibrotic liver tissue is largely devoid of DNA CNAs, highly frequently occurring DNA CNAs are found in mouse tumors, which is indicative of a profound increase in chromosomal instability in HCC. When compared to CNAs in human HCC, we found that 33% of genes in these segments are similarly affected in the mouse tumors. Our results suggest that CNAs most commonly arise in neoplastic tissue rather than in fibrotic liver, and demonstrate the utility of this mouse model in replicating the molecular features of human HCC. Genomic DNA was extracted from frozen liver samples from vehicle-control and DEN+CCl4-treated mice using a DNEasy kit (Qiagen, Valencia, CA). Eighteen mouse tumor samples were included in the study, as well as 18 matched non-tumor samples taken from fibrotic, non-tumorous, surrounding liver tissue from the same mice. Liver DNA from 6 vehicle control-mice was pooled and used as the reference genome in the aCGH experiments. Copy number alterations were identified using the normalized data.
2015-11-01 | E-GEOD-71849 | biostudies-arrayexpress
Project description:A large fraction of HCC in Peru arises in younger, non-cirrhotic patients. Global DNA methylation analysis of the HCC and non-tumor liver (NTL) tissues demostrate a profound overhaul of the developmental DNA methylation programme culminating in an global hyper-methylated pattern in HCC. We used microarrays to compare global DNA methylation between tumor and non-tumor liver tissues and identified CpGs and ontologies that are distinctively differentially methylated between subsets.
2021-01-31 | GSE136380 | GEO