Project description:There are significant differences in the expression of genes that regulate metabolic pathways in HCC as compared to Cirrhosis or non-tumor liver tissues. These charcteristic pathways can be exploited for metabolic imaging biomarkers of HCC. We used microarrays to perform genome-wide association study expression in human Grade III hepatocellular carcinoma and surrounding tissues.
Project description:Hepatocellular carcinoma (HCC) is the fifth most-common cancer worldwide causing nearly 600,000 deaths esch year. Approximately 80% of HCC develops on the background of cirrhosis.It is necessary to identify novel genes involved in HCC to implement new diagnostic and treatment options. However, the molecular pathogenesis of HCC largely remains unsolved. Only a few genetic alterations, namely those affecting p53, β-catenin and p16INK4a have been implicated at moderate frequencies of these cancers. Early detection of HCC with appropriate treatment can decrease tumor-related deaths We used microarrays to detail the global programme of gene expression profiles of cirrhosis and tumor liver samples. 15 cirrhosis and 15 HCC samples were collected with informed constent of each patient. Surgically resected tissues were snap frozen in liquid nitrogen and stored at -80C, and subjected to RNA extraction. Histology slides were prepared for all samples and scored by an experienced scientist. For the tumor samples, tissues were resected from inside the tumor, while tissues were resected from adjacent tissue sorrounding the tumor for non-tumor samples.
Project description:The role of chronic hepatitis C virus (HCV) in the pathogenesis of HCV-associated hepatocellular carcinoma (HCC) is not completely understood, particularly at the molecular level. We studied gene expression in normal, pre-malignant (cirrhosis), and tumor (HCC) liver tissues using Affymetrix GeneChips. Keywords: cross-sectional
Project description:Background: Several studies have investigated the association of miRNAs with hepatocellular carcinoma (HCC) but the data are not univocal. Methods: We performed a microarray study of miRNAs in hepatitis C virus (HCV)-associated HCC and other liver diseases and healthy conditions. Results and Conclusions: The simultaneous comparison of different liver diseases and normal livers allowed the identification of 18 miRNAs exclusively expressed in HCV-associated HCC, with sensitivity and specificity values of diagnostic-grade. A total number of 76 liver specimens obtained from 43 patients were analyzed: 26 liver specimens obtained from 10 patients with HCV-associated HCC, including 9 specimens from the tumor area (HCC) and 17 specimens from the surrounding non-tumorous tissue affected by cirrhosis (HCC-CIR); 18 specimens from 10 patients with HCV-associated cirrhosis without HCC (CIR); 13 specimens from 4 patients with HBV-associated acute liver failure (ALF); 12 specimens from 12 liver donors (LD); and 7 from normal liver of 7 subjects who underwent hepatic resection for liver angioma (NL).
Project description:The role of chronic hepatitis C virus (HCV) in the pathogenesis of HCV-associated hepatocellular carcinoma (HCC) is not completely understood, particularly at the molecular level. We studied gene expression in normal, pre-malignant (cirrhosis), and tumor (HCC) liver tissues using Affymetrix GeneChips. Experiment Overall Design: Liver tissue samples were obtained from patients waiting for liver transplantation at one of the GR2HCC Centers. Additionally, normal liver and tumor samples were also obtained from the Liver Tissue Cell Distribution System. For each sample, RNA was extracted and hybridized to an Affymetrix GeneChip.
Project description:We evaluated the expression of known human miRNAs in human hepatocellular carcinoma (HCC) and normal hepatic tissues from southeast China, and identified the differentially expressed miRNAs in HCC tissues. We use microRNA array platform from CapitalBio Corp. to access the miRNA expression profiles in HCC and non-tumor liver samples from Southeast China. There were 5 HCC samples and 3 non-tumor liver samples in our study. As the microarray platform we used was based on a older version of miRBase, we mapped the probe sequences to a newer version of miRBase before these data was applied to further analysis.
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:miRNA played an important role in the process of carcinogenesis in HBV related hepatocellular carcinoma. Therefore, we performed miRNA microarray to evaluate the miRNAs that expressed differentially between HCC tumor versus non-tumor liver tissues. RNA was extracted from snap fresh tissue collected from resected HCC tumor and adjacent non-tumor liver tissues. All HCC tumors were HBV-associated HCC.
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.
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.