Disseminative Recurrence Signature for hepatocellular carcinoma from non-alcoholic fatty liver disease
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ABSTRACT:
PROVIDER: PRJNA885407 | ENA |
REPOSITORIES: ENA
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Project description:Non-alcoholic fatty liver disease (NAFLD) is a major global health problem with its high prevalence and risk of developing lethal complications, progressive liver fibrosis and hepatocellular carcinoma (HCC), the only rising cancer mortality in the U.S. Ever after curative surgical resection, HCC can recur at extremely high rate (70% within 5 years); therefore, prediction of recurrent HCC is expected to guide decision of neo/adjuvant therapies currently under active development. Herein, we derived an HCC-transcriptome-based signature to predict disseminative recurrence, which originates from disseminated HCC cells from surgically resected initial tumor, and validated it in an independent cohort.
2023-09-14 | GSE214432 | GEO
Project description:Transcriptome profile of hepatocellular carcinoma from non-alcoholic fatty liver.
| PRJNA885397 | ENA
Project description:Non-alcoholic fatty liver (NAFL) has the potential to progress to non-alcoholic steatohepatitis (NASH) or to promote type 2 diabetes mellitus (T2DM). However, NASH and T2DM do not always develop coordinately. We established rat models of NAFL, NASH, and NAFL + T2DM to recapitulate different phenotypes associated with NAFLD and its progression. Microarrays were used to identify hepatic gene expression changes in each of these models. The goal is to identify a predictor of different NAFLD progressions. Non-alcoholic fatty liver disease (NAFLD) is recognized as a low-grade systemic inflammatory state with both hepatic and extra-hepatic manifestations. We aimed to identify common key regulators and adaptive pathways in different NAFLD phenotypes. NAFL, NASH and NAFL+T2DM rat models were used to represent simple fatty liver, fatty liver with severe hepatic manifestations, and fatty liver with severe metabolic manifestations, respectively. We applied microarray analysis to characterize the key regulators and adaptive pathways in different NAFLD phenotypes. There are 12 samples in our study which belonged to 4 groups, and each group contains 3 different samples.
2015-01-23 | E-GEOD-65220 | biostudies-arrayexpress
Project description:Background: Liver transplantation (LT) for Hepatocellular carcinoma (HCC) can be offered to patients beyond Milan criteria. However, there are currently no molecular markers that can be used on HCC explant histology to predict recurrence, which arises in up to 20% of LT recipients. The goal of our study was to identify proteins on HCC explant predictive of recurrence post-transplant, thereby guiding surveillance strategies and identifying patients beyond Milan criteria who would fare well following LT. Methods: LT recipients who had been transplanted at the University Health Network for HCC beyond Milan criteria in the context of Hepatitis B cirrhosis were identified. Snap-frozen samples from the dominant tumors of recurrent (N=7) and non-recurrent (N=4) patients were analyzed using LC-MS/MS on a Q-Exactive Plus mass spectrometer to delineate a distinctive proteomic signature. These tumors were also profiled by a Human Gene 2.0 ST microarray platform to identify a transcriptomic signature predictive of recurrence and analyzed with R packages. STRING database was used to characterize the implicated pathways. Kaplan-Meier estimator was used to generate a combined proteomic/transcriptomic signature predictive of HCC recurrence in patients with HCC beyond Milan criteria at time of LT. Significantly predictive proteins were verified and internally validated by immunoblotting or immunohistochemistry. Results: A total of 79 proteins and 636 genes were significantly differentially expressed in recurrent HCC, compared to non-recurrent (p<0.05). Among these, LGALS3, LGALS3BP, HAL, THBS1, and BLMH, were significantly increased in recurrent HCC at the protein and gene expression level. In turn, ALDH1A1 protein and gene expression were significantly decreased in recurrent HCC. Univariate survival analysis depicted ALDH1A1 (HR=0.084, 95%CI 0.01-0.68, p=0.02), LGALS3BP (HR=7.14, 95%CI 1.20-42.96, p=0.03), and LGALS3 (HR=2.89, 95%CI 1.01-8.3, p=0.049) as the key dysregulated proteins and genes in the patients with HCC recurrence versus those with non-recurrence by both proteomic and transcriptomic analysis. Decreased ALDH1A1 and significantly increased LGALS3 protein expression in recurrent HCC was verified by immunoblotting. Increased LGALS3BP protein expression in recurrent HCC was orthogonally verified and validated by immunohistochemistry in 30 independent HCC samples. Conclusion: Protein and gene expression of the cancer stem cell marker ALDH1A1 was protective against cancer recurrence in patients transplanted for HCC beyond Milan criteria. Conversely, increased expression of LGALS3 and LGALS3BP on explant was significantly predictive of post-transplant recurrence. These findings were internally validated, suggesting potential utility in identifying patients with HCC beyond Milan who would clearly benefit from transplant with limited recurrence risk and guiding post-transplant surveillance.
2022-02-22 | PXD022881 | Pride
Project description:Global gene expression patterns of 2 human steatosis and 9 human non-alcoholic steatohepatitis (NASH) together with their respective control patterns were analyzed to define the non-alcoholic fatty liver disease (NAFLD) progression molecular characteristics and to define NASH early markers from steatosis. Human liver samples of steatosis and non-alcoholic steatohepatitis were selected for RNA extraction and hybridization on Affymetrix microarrays. This dataset is part of the TransQST collection.
2014-11-07 | E-GEOD-63067 | biostudies-arrayexpress
Project description:The molecular features of hepatocellular carcinoma arising from non-alcoholic fatty liver disease (NAFLD-HCC) are not well known. In this study, we investigated the mechanism by which NAFLD-HCC survives in a fat-rich environment. We found that caveolin (CAV)-1 was overexpressed in clinical specimens from NAFLD-HCC patients. HepG2, HLE, and HuH-7 HCC cell lines showed decreased proliferation in the presence of the saturated fatty acids palmitic acid and stearic acid, although only HLE cells expressed high levels of CAV-1. HLE cells treated with oleic acid (OA) showed robust proliferation, whereas CAV-null HepG2 cells showed reduced proliferation and increased apoptosis. CAV-1 knockdown in HLE cells attenuated the OA-induced increase in proliferation and enhanced apoptosis. Liquid chromatography-tandem mass spectrometry analysis revealed that the levels of OA-containing ceramide, a pro-apoptotic factor, were higher in HepG2 and CAV-1-deficient HLE cells than in HLE cells, suggesting that CAV-1 inhibits apoptosis by decreasing the level of OA-containing ceramide. These results indicate that CAV-1 is important for NAFLD-HCC survival in fatty acid-rich environments and is a potential therapeutic target.
2017-05-23 | GSE99131 | GEO
Project description:The DNA methylation value in early-stage hepatocellular carcinoma was undetermined. The Illumina Infinium 450k Human DNA methylation Beadchip was used to identify recurrence-related abbrent CpG methylation. This study was performed in a total of 66 early-stage HCC samples, including 29 recurrence samples and 37 recurrence-free samples
2017-04-30 | E-GEOD-75041 | biostudies-arrayexpress
Project description:While we and others have uncovered and validated several genomic predictors for metastatic recurrences, a molecular or genomic predictor that can reliably identify high-risk patients for late de novo recurrence has not been firmly established. We analyzed previously reported gene expression data from human livers that underwent partial hepatectomy or transplantation, which were representative physiological conditions that trigger liver regeneration signals. We generated gene expression data from tumor and matched non-tumor surrounding tissues of 72 hepatocellular carcinoma (HCC) patients who underwent surgical resection as the primary treatment. We used these gene expression data to develop a new prognostification model for recurrence of HCC after surgery. We generated gene expression data from tumor and matched non-tumor surrounding tissues of 72 HCC patients who underwent surgical resection as the primary treatment.
2014-11-03 | E-GEOD-39791 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-09-29 | GSE214435 | GEO
Project description:While we and others have uncovered and validated several genomic predictors for metastatic recurrences, a molecular or genomic predictor that can reliably identify high-risk patients for late de novo recurrence has not been firmly established. We analyzed previously reported gene expression data from human livers that underwent partial hepatectomy or transplantation, which were representative physiological conditions that trigger liver regeneration signals. We generated gene expression data from tumor and matched non-tumor surrounding tissues of 72 hepatocellular carcinoma (HCC) patients who underwent surgical resection as the primary treatment. We used these gene expression data to develop a new prognostification model for recurrence of HCC after surgery.
2014-11-03 | GSE39791 | GEO