Project description:We applied small RNA Solexa sequencing technology to identify microRNA expression in human liver samples from surgically removed liver tissues including three normal liver tissues (distal normal liver tissue of liver hemangioma), an hepatitis B virus (HBV)-infected liver, a severe chronic hepatitis B liver, two HBV-related hepatocellular carcinoma (HCC), an hepatitis C virus (HCV)-related HCC, and an HCC without HBV or HCV infection. All samples were collected with the informed consent of the patients and the experiments were approved by the ethics committee of Second Military Medical University, Shanghai, China. We investigated the miRNome in human normal liver and suggested some deregulated abundantly expressed microRNAs in HCC. center_name: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China. Examination of miRNome in human liver samples from surgically removed liver tissues including three normal liver tissues (distal normal liver tissue of liver hemangioma), an hepatitis B virus (HBV)-infected liver tissue, a severe chronic hepatitis B liver tissue, an HBV-related hepatocellular carcinoma (HCC) tissue and adjacent liver tissues of different regions,an HBV-related HCC tissue and adjacent liver tissue, an hepatitis C virus (HCV)-related HCC tissue and adjacent liver tissue, and an HCC without HBV or HCV infection and adjacent liver tissue. All 15 human liver tissue samples.
Project description:FBXL6 is frequently over-expressed in human hepatocellular carcinoma (HCC). However, it is still unknown the underlying mechanisms by which FBXL6 promotes HCC. In this study, we compared ubiquitinated protein profiles among a panel of liver tissue samples (including HCC, adjacent tissues and normal tissues) from Fbxl6LSL-fl/+; Alb-cre mice and Alb-cre mice by proteomics and ubiquitomics analysis. There are many proteins with ubiquitination in FBXL6 overexpressed HCC, suggesting ubiquitination may play a critical role in FBXL6-mediated HCC. A1--- normal tissue 1 A2--- normal tissue 2 B1--- Adjacent tissue 1 B2--- Adjacent tissue 2 C1--- HCC tissue 1 C2--- HCC tissue 2
Project description:<p>Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare liver tumor primarily affecting adolescents and young adults. Little is known of the molecular pathogenesis. To characterize the disease we performed RNA sequencing and whole genome sequencing on FL-HCC tumors and adjacent normal tissue. The results demonstrate few consistent differences on the chromosomal level and many hundreds of alterations in the expression of RNA transcripts.</p>
Project description:HLA class I ligandome dataset obtained from hepatocellular carcinoma (HCC) as well as corresponding adjacent benign liver tissue (n=16) characterizing respective HLA immunoprecipitates. Additionally, from a subset of the mentioned HCC/ adjacent benign liver samples datasets gained from shotgun protein identification, comprising HCC as well as adjacent benign liver tissue (n=7) are provided. Further, for one patient shotgun protein identification was also performed in serum (blood) samples obtained after HCC recurrence.
Project description:The cell of origin of hepatoblastoma in humans and mice (HB) is unknown; it has been hypothesized to be a transformed hepatocyte, an oval cell, or a multipotent hepatic progenitor cell. In mice, the current dogma is that HBs arise within hepatocellular neoplasms as a result of further transformation from a neoplastic hepatocyte. However, there is little evidence in the literature to support a direct relationship between these two cell types. Furthermore, due to differences in etiology and development of hepatoblastoma between mice and humans, many have questioned the relevance of these tumors in hazard identification and risk assessment. In order to better understand the relationship between hepatocellular carcinoma and hepatoblastoma, as well as better determine the molecular similarities between mouse and human hepatoblastoma, global gene expression analysis and targeted Hras and Ctnnb1 mutation analysis were performed using concurrent hepatoblastoma, hepatocellular carcinoma, and associated normal adjacent liver (in the context of vehicle control liver) samples from a recent National Toxicology Program chronic bioassay. The data from this study provides a better understanding of the origins of hepatoblastoma in the B6C3F1 mice and the relevance of mouse hepatoblastoma to humans when considering chemical exposures of potential human cancer risk. Compare mouse hepatoblastoma versus adjacent hepatocellular carcinomas versus adjacent non-tumor liver and vehicle control normal liver, 6 replicates each group.
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.
Project description:To study its expression and regulatory functions in hepatocellular carcinoma (HCC) progression, whole transcriptome RNA sequencing in paired HCC tumor and adjacent non-tumor liver tissue samples from 3 local Hispanic patients was performed.
Project description:Sex differences in liver gene expression are dictated by sex-differences in circulating growth hormone (GH) profiles. Presently, the pituitary hormone dependence of mouse liver gene expression was investigated on a global scale to discover sex-specific early GH response genes that might contribute to sex-specific regulation of downstream GH targets and to ascertain whether intrinsic sex-differences characterize hepatic responses to plasma GH stimulation. RNA expression analysis using 41,000-feature microarrays revealed two distinct classes of sex-specific mouse liver genes: genes subject to positive regulation (class-I) and genes subject to negative regulation by pituitary hormones (class-II). Genes activated or repressed in hypophysectomized (Hypox) mouse liver within 30-90min of GH pulse treatment at a physiological dose were identified as direct targets of GH action (early response genes). Intrinsic sex-differences in the GH responsiveness of a subset of these early response genes were observed. Notably, 45 male-specific genes, including five encoding transcriptional regulators that may mediate downstream sex-specific transcriptional responses, were rapidly induced by GH (within 30min) in Hypox male but not Hypox female mouse liver. The early GH response genes were enriched in 29 male-specific targets of the transcription factor Mef2, whose activation in hepatic stellate cells is associated with liver fibrosis leading to hepatocellular carcinoma, a male-predominant disease. Thus, the rapid activation by GH pulses of certain sex-specific genes is modulated by intrinsic sex-specific factors, which may be associated with prior hormone exposure (epigenetic mechanisms) or genetic factors that are pituitary-independent, and could contribute to sex-differences in predisposition to liver cancer or other hepatic pathophysiologies.