Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA120097 | ENA |
REPOSITORIES: ENA
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Project description:Background/Aims: Recurrence-free survival (RFS) following curative resection of hepatocellular carcinoma (HCC) in subjects with hepatitis C virus (HCV) infection is highly variable. Traditional clinico-pathological endpoints are recognized as weak predictors of RFS. It has been suggested that gene expression profiling of HCC and nontumoral liver tissue may improve prediction of RFS, aid in understanding of the underlying liver disease, and guide individualized therapy. The goal of this study was to create a gene expression predictor of HCC recurrence in subjects with HCV. Methods: Frozen samples of the tumors and nontumoral liver were obtained from 47 subjects with HCV-associated HCC. Additional nontumoral liver samples were obtained from HCV-free subjects with metastatic liver tumors. Gene expression profiling data was used to determine the molecular signature of HCV-associated HCC and to develop a predictor of RFS. Results: The molecular profile of the HCV-associated HCC confirmed central roles for MYC and TGF-beta1 in liver tumor development. Gene expression in tumors was found to have poor predictive power with regards to RFS, but analysis of nontumoral tissues yielded a strong predictor for RFS in late-recurring (>1 year) subjects. Importantly, nontumoral tissue-derived gene expression predictor of RFS was highly significant in both univariable and multivariable Cox proportional hazard model analyses. Conclusions: Microarray analysis of the nontumoral tissues from subjects with HCV-associated HCC delivers novel molecular signatures of RFS, especially among the late-recurrence subjects. The gene expression signature of the predictor gives important insights into the pathobiology of HCC recurrence and used in design of the individualized therapy. 43 tumor (JT) and 44 non-tumor (JNT) liver tissues surgically resected from patients with HCV-associated hepatocellular carcinoma; 8 non-tumor liver tissues (control samples, JC) surgically resected from HCV- or HBV-free patients with metastatic liver tumor. Inter-batch normalization was carried out using Distance Weighted Discrimination procedure. The supplementary file 'GSE17856_Readme.txt' contains a description of the replicates used for normalization. The 'GSE17856_US14702406_2514850*' files are the raw data files for the replicates.
2010-04-14 | E-GEOD-17856 | biostudies-arrayexpress
Project description:Background/Aims: Recurrence-free survival (RFS) following curative resection of hepatocellular carcinoma (HCC) in subjects with hepatitis C virus (HCV) infection is highly variable. Traditional clinico-pathological endpoints are recognized as weak predictors of RFS. It has been suggested that gene expression profiling of HCC and nontumoral liver tissue may improve prediction of RFS, aid in understanding of the underlying liver disease, and guide individualized therapy. The goal of this study was to create a gene expression predictor of HCC recurrence in subjects with HCV. Methods: Frozen samples of the tumors and nontumoral liver were obtained from 47 subjects with HCV-associated HCC. Additional nontumoral liver samples were obtained from HCV-free subjects with metastatic liver tumors. Gene expression profiling data was used to determine the molecular signature of HCV-associated HCC and to develop a predictor of RFS. Results: The molecular profile of the HCV-associated HCC confirmed central roles for MYC and TGF-beta1 in liver tumor development. Gene expression in tumors was found to have poor predictive power with regards to RFS, but analysis of nontumoral tissues yielded a strong predictor for RFS in late-recurring (>1 year) subjects. Importantly, nontumoral tissue-derived gene expression predictor of RFS was highly significant in both univariable and multivariable Cox proportional hazard model analyses. Conclusions: Microarray analysis of the nontumoral tissues from subjects with HCV-associated HCC delivers novel molecular signatures of RFS, especially among the late-recurrence subjects. The gene expression signature of the predictor gives important insights into the pathobiology of HCC recurrence and used in design of the individualized therapy.
2010-04-14 | GSE17856 | GEO
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.
2010-04-10 | E-GEOD-21279 | biostudies-arrayexpress
Project description:BACKGROUND & AIMS: Expression of microRNAs (miRNAs) in metastatic foci of hepatocellular carcinoma (HCC) is unknown. We identified metastasis-related miRNAs in recurrent cases after living donor liver transplantation (LDLT). Methods: We performed a comprehensive analysis of primary HCC (T), noncancerous liver (N), and resected recurrent (metastatic) HCC (M) using microarray analyses to identify metastasis-related miRNAs in in three patients with post-transplant recurrence. The RNA samples from three cases that underwent resection of recurrences after LDLT were made available for miRNA microarray analysis. The three cases included a 57-year-old man (case 1) with peritoneal recurrence and infected by hepatitis B virus (HBV), and a 48-year-old woman (case 2) and a 51-year-old man (case 3) with lung recurrences and hepatitis C virus (HCV) infection. Microarray analysis was performed for each RNA sample from the (T), (N) in the explanted liver, and (M). A sample containing equal amounts of RNAs from histologically normal livers of three living donors (NL: normal liver) was analyzed as a control. The RNA samples from three cases that underwent resection of recurrences after living donor liver transplantation were made available for microRNA microarray analysis. Microarray analysis was performed for each RNA sample from the primary HCC (T), noncancerous liver (N) in the explanted liver, and resected recurrent metastatic HCC (M). A sample containing equal amounts of RNAs from histologically normal livers of three living donors (NL: normal liver) was analyzed as a control.
2013-10-25 | E-GEOD-41874 | biostudies-arrayexpress
Project description:Gene expression profiling of hepatocellular carcinoma (HCC) and background liver has been studied extensively; however, the relationship between the gene expression profiles of different lesions has not been assessed. We examined the expression profiles of 34 HCC specimens (17 hepatitis B virus [HBV]-related and 17 hepatitis C virus [HCV]-related) and 71 non-tumor liver specimens (36 chronic hepatitis B [CH-B] and 35 chronic hepatitis C [CH-C]) using an in-house cDNA microarray consisting of liver-predominant genes. Graphical Gaussian modeling (GGM) was applied to elucidate the interactions of gene clusters among the HCC and non-tumor lesions. Gene expression profiling of HCC and non-tumor lesions revealed the predisposing changes of gene expression in HCC. This approach has potential for the early diagnosis and possible prevention of HCC. We examined the expression profiles of 34 HCC specimens (17 hepatitis B virus [HBV]-related and 17 hepatitis C virus [HCV]-related) and 71 non-tumor liver specimens (36 chronic hepatitis B [CH-B] and 35 chronic hepatitis C [CH-C]) using an in-house cDNA microarray consisting of liver-predominant genes. Graphical Gaussian modeling (GGM) was applied to elucidate the interactions of gene clusters among the HCC and non-tumor lesions.
2013-11-14 | E-GEOD-44074 | biostudies-arrayexpress
Project description:In this study, we utilized microRNA expression profiling to assess risk of HCC recurrence after liver resection. We examined microRNA expression profiling in paired tumor and non-tumor liver tissues of 73 HCC patients with mild cirrhosis (Child-Pugh A/B) who satisfy Milan Criteria. We constructed prediction models of recurrence-free survival using Cox proportional hazard model and principal component analysis.
2011-02-08 | E-GEOD-21362 | biostudies-arrayexpress
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.
2010-04-10 | GSE21279 | GEO
Project description:The post-translational modification of lysine acetylation is related to hepatocellular carcinoma (HCC), and understanding this relationship requires detailed knowledge about the acetylated proteome in HCC tissue and about differences in protein acetylation between cirrhosis and liver cancer. Here we characterized the acetylome in three paired sets of cirrhotic tissue and hepatitis B-related HCC tissue. Combining affinity-based enrichment of acetylated peptides with highly sensitive mass spectrometry, we identified 1493 acetylation sites in 777 proteins and quantified 1040 acetylation sites in 587 proteins. We discovered that the histone acetyltransferases p300 and CBP were hyperacetylated in HCC and cirrhosis but not in normal liver tissue. We also identified several proteins acetylated at more than 10 lysines in HCC and cirrhosis. In addition, our results revealed that HCC was associated with up-regulation of acetylation at 353 sites in 237 proteins and down-regulation of acetylation at 209 sites in 122 proteins. We validated our results using western blotting and immunohistochemistry. Validation with an independent set of clinical samples confirmed our initial screening result that acetylation of lysine 120 in histone H2B type 1-C/E/F/G/I and lysine 18 in histone H3.3 was significantly associated with survival of HCC patients. Acetylation of lysine 77 in histone H4 was associated with survival as well as recurrence. Our study provides numerous new leads to examine the role of acetylation in HCC and its potential as a prognostic marker as well as therapeutic target.
2021-09-08 | PXD014994 | Pride
Project description:BACKGROUND & AIMS: Expression of microRNAs (miRNAs) in metastatic foci of hepatocellular carcinoma (HCC) is unknown. We identified metastasis-related miRNAs in recurrent cases after living donor liver transplantation (LDLT). Methods: We performed a comprehensive analysis of primary HCC (T), noncancerous liver (N), and resected recurrent (metastatic) HCC (M) using microarray analyses to identify metastasis-related miRNAs in in three patients with post-transplant recurrence. The RNA samples from three cases that underwent resection of recurrences after LDLT were made available for miRNA microarray analysis. The three cases included a 57-year-old man (case 1) with peritoneal recurrence and infected by hepatitis B virus (HBV), and a 48-year-old woman (case 2) and a 51-year-old man (case 3) with lung recurrences and hepatitis C virus (HCV) infection. Microarray analysis was performed for each RNA sample from the (T), (N) in the explanted liver, and (M). A sample containing equal amounts of RNAs from histologically normal livers of three living donors (NL: normal liver) was analyzed as a control.
2013-10-25 | GSE41874 | GEO
Project description:Background and aims: Liver transplantation (LT) is the most radical treatment for hepatocellular carcinoma (HCC) with high rates of long-term survival, but tumor recurrence after LT is an unresolved problem. The aim of our study was to identify predictive markers for tumor recurrence after liver transplantation. Methods: In a retrospective single-center study, we included all patients with LT for HCC in our institution (01/2007-12/2012). Beside demographic data, we analyzed course, bridging therapies, Serum-AFP, time point of tumor recurrence, as well as the correlation of imaging and histopathology of our recipients. Additionally, we performed a microarray analysis to identify different miRNA profiles of patients with and without HCC recurrence after LT. Single assay stem-loop real-time PCR (Q-RT-PCR) was used for validation of the results. Results: During the study period, we performed 92 LT in patients with HCC (22 women, 70 men). Twenty-two (23.9%) patients developed a recurrent HCC after LT. Our subgroup with tumor recurrence after LT, presented with a mean disease-free survival of 10 months (3-55 months) and an overall survival of 25.5 months (4-77 months). Milan criteria, AFP levels and pathologic grading had an influence on the tumor recurrence. Performing miRNA analysis, we could identify significant upregulation of 8 miRNAs and downregulation of another 5 miRNAs in patients with tumor recurrence. Consecutively, array data were successfully validated using Q-RT-PCR. Multivariate Cox regression, ROC analysis and Kaplan-Meier showed that a score consisting of two miRNAs and Milan criteria are an independent predictor for tumor recurrence-free survival. Conclusions: Despite careful selection of patients, an early recurrence of HCC after LT cannot be avoided completely. Reliable prognostic markers related to tumor biology are still missing. Analysis and validation of specific miRNAs combined with radiological parameters might lead to a promising strategy for the prediction of tumor recurrence, but prospective studies have to follow. 8 macrodissected hepatocellular carcinoma (recurrent HCC) and 10 macrodissected hepatocellular carcinoma (non-recurrent HCC).
2016-03-01 | E-GEOD-64989 | biostudies-arrayexpress