Project description:We report the application of RNA sequencing technology for high-throughput profiling in HCC tissues. In the present study, to explore novel biomarkers of HCC, we firstly explored the expression profiles of mRNAs and miRNAs in three pairs of HCC patients (tumor tissues and non-tumorous tissues) by high-throughput RNA sequencing. A total of 1024 mRNAs were found to be significantly dysregulated (636 up-regulated and 388 down-regulated), 50 miRNAs were found to be significantly dysregulated (27 up-regulated and 23 down-regulated) in the HCC tissues compared with the non-tumorous tissues.Then validae the differentially expressed miRNAs by qRT-PCR in HCC tissues and serum. This study provides a framework for the application of miRNAs to be ideal biomarkers for HCC.
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tissue was highly effective: samples from 90% of the patients yielded data of high quality, including samples that had been archived for more than 24 years.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.
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:High frequency of loss of heterozygosity (LOH) at locus D4S2964 was found in hepatocellular carcinoma (HCC) by our previous studies and others’. The present study was designed to explore genes around the locus affected by LOH and their clinical implications. 440 SNPs located at 49 genes around D4S2964 were selected from NCBI website for the SNPs microarray fabrication. LOH of these SNPs markers in 112 cases of HCC tissues and paired adjacent liver tissues were investigated by the SNP microarray. A map of LOH of SNPs in genes around D4S2964 was constructed. 112 pairs of HCC tissues and corresponding non-tumor tissues was genotyped. LOH and its clinical implication was analyzed.
Project description:Integrin alpha 6 (ITGA6) forms integrin receptors with either integrin β1 (ITGB1) or integrin beta 4 (ITGB4). 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 ten local Hispanic patients was performed. The average expression of ITGA6 was found increased by over 3.5-fold in HCC tumor tissues in comparison with their adjacent non-tumor tissues. The study indicates integrin alpha6-beta4 complex as a potential therapeutic target for treating patients in HCC.
Project description:Epigenetic changes commonly occur in hepatocellular carcinoma (HCC) and are associated with aberrant gene expression. Recently, we demonstrated the pivotal role of abnormal H3K4me3 methylation, which is catalyzed by the menin/MLL, a TrxG family, in HCC development. Meanwhile, there is clear evidence that increasing global levels of H3K27me3 are activated in human primary HCC. To further elucidate the functional relatedness of the active H3K4me3 and repressive H3K27me3 histone remodeling in HCC, we performed H3K4me3 and H3K27me3 ChIP-on-chip screen using three HCC specimens and their adjacent tissues. Comparison of ChIP-on-chip results between tumor(C) and adjacent tissues(N) from three HCC specimens with H3K4me3
Project description:Epigenetic changes commonly occur in hepatocellular carcinoma (HCC) and are associated with aberrant gene expression. Recently, we demonstrated the pivotal role of abnormal H3K4me3 methylation, which is catalyzed by the menin/MLL, a TrxG family, in HCC development. Meanwhile, there is clear evidence that increasing global levels of H3K27me3 are activated in human primary HCC. To further elucidate the functional relatedness of the repressive H3K27me3 and active H3K4me3 histone remodeling in HCC, we performed H3K27me3 and H3K4me3 ChIP-on-chip screen using three HCC specimens and their adjacent tissues. Comparison of ChIP-on-chip results between tumor(C) and adjacent tissues(N) from three HCC specimens with H3K27me3
Project description:We analyzed the proteome of tumor and matched non-tumor biopsies from 51 treatment-naive Hepatocellular carcinoma (HCC) patients by DIA (SWATH). Thereby we aim to find subgroups of patients characterized by specific pathway activation. Furthermore, we aim to find novel factors involved in HCC development and novel biomarkers.
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.