Serum glycoprotein markers in non-alcoholic steatohepatitis and hepatocellular carcinoma
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Agilent 6495B QQQ mass spectrometer
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Prasanna Ramachandran
PROVIDER: MSV000088809 | MassIVE | Wed Feb 09 12:20:00 GMT 2022
REPOSITORIES: MassIVE
Publications
Serum Glycoprotein Markers in Nonalcoholic Steatohepatitis and Hepatocellular Carcinoma.
Ramachandran Prasanna P Xu Gege G Huang Hector H HH Rice Rachel R Zhou Bo B Lindpaintner Klaus K Serie Daniel D
Journal of proteome research 20220314 4
Fatty liver disease progresses through stages of fat accumulation and inflammation to nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis, and eventually hepatocellular carcinoma (HCC). Currently available diagnostic tools for HCC lack sensitivity and specificity. In this study, we investigated the use of circulating serum glycoproteins to identify a panel of potential prognostic markers that may be indicative of progression from the healthy state to NASH and further to HCC. Serum sample ...[more]
Similar Datasets
Project description:Cirrhosis is an emerging major cause of the development of hepatocellular carcinoma (HCC), but in non-alcoholic fatty liver disease (NAFLD), up to 50% of patients with HCC had no clinical or histological evidence of cirrhosis. It is currently challenging to propose general recommendations for screening patients with NAFLD without cirrhosis, and each patient should be evaluated on a case-by-case basis based on the profile of specific risk factors identified. For HCC screening in NAFLD, a valid precision-based screening is needed. Currently, when evaluating this population of patients, the use of non-invasive methods can guide the selection of those who should undergo a screening and surveillance program. Hence, the objective of the present study is to review the epidemiology, the pathophysiology, the histopathological aspects, the current recommendations, and novel perspectives in the surveillance of non-cirrhotic NAFLD-related HCC.
| S-EPMC9846942 | biostudies-literature
Project description:Increased prevalence of non-alcoholic fatty liver disease (NAFLD) is one of the consequences of the current obesity epidemic. NAFLD is a major form of chronic liver disease that is highly prevalent in obese and overweight adults and children. Nonalcoholic steatohepatitis (NASH) is the severe form of NAFLD, and uncontrolled inflammation as displayed in NASH has been identified as one of the key events in enhancing hepatic carcinogenesis. Lycopene is a non-provitamin A carotenoid and the pigment principally responsible for the characteristic deep-red color of ripe tomato and tomato products, as well as some fruits and vegetables. Lycopene's innate antioxidant and anti-inflammatory properties have generated research interests on its capacity to protect against human diseases that are associated with oxidative stress and inflammation. In addition, differential mechanisms of lycopene metabolism including endogenous cleavage by carotenoid cleavage oxygenases (BCOs), generate lycopene metabolites that may also have significant impact on human disease development. However, it remains to be elucidated as to whether lycopene or its metabolites apolycopenoids have protective effects against obesity-related complications including inflammation and tumorigenesis. This article summarizes the in vivo experiments that elucidated molecular mechanisms associated with obesity-related hepatic inflammation and carcinogenesis. This review also provides an overview of lycopene metabolism, and the molecular pathways involved in the potential beneficial properties of lycopene and apolycopenoids. More research is clearly needed to fully unravel the importance of BCOs in tomato carotenoid metabolism and the consequence on human health and diseases.
| S-EPMC3916853 | biostudies-other
Project description:Non-alcoholic steatohepatitis (NASH) is a chronic and progressive form of non-alcoholic fatty liver disease (NAFLD). Its global incidence is increasing which makes NASH an epidemic and a public health threat. Due to repeated insults to the liver, patients are at risk for developing hepatocellular carcinoma (HCC). The progression of NASH to HCC was initially defined according to a two-hit model which involved the development of steatosis, followed by lipid peroxidation and inflammation. However, current research defines a "multi-hit" or "multi-parallel hit" model which synthesizes several contributing pathways involved in progressive fibrosis and oncogenesis. This perspective considers the effects of cellular, genetic, immunologic, metabolic, and endocrine pathways leading up to HCC which underscores the complexity of this condition. This article will provide an updated review of the pathogenic mechanisms leading from NASH to HCC as well as an exploration of the role of biomarkers and screening.
| S-EPMC7918599 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is now the fifth cancer of greatest frequency and the second leading cause of cancer related deaths worldwide. Chief amongst the risks of HCC are hepatitis B and C infection, aflatoxin B1 ingestion, alcoholism and obesity. The latter can promote non-alcoholic fatty liver disease (NAFLD), that can lead to the inflammatory form non-alcoholic steatohepatitis (NASH), and can in turn promote HCC. The mechanisms by which NASH promotes HCC are only beginning to be characterized. Here in this review, we give a summary of the recent findings that describe and associate NAFLD and NASH with the subsequent HCC progression. We will focus our discussion on clinical and genomic associations that describe new risks for NAFLD and NASH promoted HCC. In addition, we will consider novel murine models that clarify some of the mechanisms that drive NASH HCC formation.
| S-EPMC4768195 | biostudies-literature
Project description:With the prevalence of hepatitis C virus expected to decline, the proportion of hepatocellular carcinoma (HCC) related to non-alcoholic steatohepatitis (NASH) is anticipated to increase exponentially due to the growing epidemic of obesity and diabetes. The annual incidence rate of developing HCC in patients with NASH-related cirrhosis is not clearly understood with rates ranging from 2.6%-12.8%. While multiple new mechanisms have been implicated in the development of HCC in NASH; further prospective long-term studies are needed to validate these findings. Recent evidence has shown a significant proportion of patients with non-alcoholic fatty liver disease and NASH progress to HCC in the absence of cirrhosis. Liver resection and transplantation represent curative therapeutic options in select NASH-related HCC patients but have placed a significant burden to our healthcare resources and utilization. Currently NASH-related HCC is the fastest growing indication for liver transplant in HCC candidates. Increased efforts to implement effective screening and preventative strategies, particularly in non-cirrhotic NASH patients, are needed to reduce the future impact imposed by NASH-related HCC.
| S-EPMC5395802 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) is the most common chronic hepatic pathology in Western countries. It encompasses a spectrum of conditions ranging from simple steatosis to more severe and progressive non-alcoholic steatohepatitis (NASH) that can lead to hepatocellular carcinoma (HCC). Obesity and related metabolic syndrome are important risk factors for the development of NAFLD, NASH and HCC. DUSP3 is a small dual-specificity protein phosphatase with a poorly known physiological function. We investigated its role in metabolic syndrome manifestations and in HCC using a mouse knockout (KO) model. While aging, DUSP3-KO mice became obese, exhibited insulin resistance, NAFLD and associated liver damage. These phenotypes were exacerbated under high fat diet (HFD). In addition, DEN administration combined to HFD led to rapid HCC development in DUSP3-KO compared to wild type (WT) mice. DUSP3-KO mice had more serum triglycerides, cholesterol, AST and ALT compared to control WT mice under both regular chow diet (CD) and HFD. The level of fasting insulin was higher compared to WT mice, though, fasting glucose as well as glucose tolerance were normal. At the molecular level, HFD led to decreased expression of DUSP3 in WT mice. DUSP3 deletion was associated with increased and consistent phosphorylation of the insulin receptor (IR) and with higher activation of the downstream signaling pathway. In conclusion, our results support a new role for DUSP3 in obesity, insulin resistance, NAFLD and liver damage.
| S-EPMC7954796 | biostudies-literature
Project description:The incidence of metabolic syndrome with fatty liver is spreading on a worldwide scale. Correspondingly, the number of patients with the hepatic phenotype of metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), and in its advanced states, non-alcoholic steatohepatitis (NASH), and the subsequent hepatocellular carcinoma (HCC) derived from NASH (NASH-HCC) is increasing remarkably. A large-scale epidemiological study revealed that obesity can be a risk factor of such cancers as HCC. Moreover, despite the ongoing trends of declining cancer incidence and mortality for most cancer types, HCC has experienced a markedly increased rate of both. Considering the differences in liver-related mortality among NAFLD patients, NASH, and NASH-HCC should be included in the objectives of initiatives to manage NAFLD patients and their progression to the advanced stages. Unfortunately, research has yet to make a crucial drug discovery for the effective treatment of NASH and NASH-HCC, although it is urgently needed. The latest widespread concept of the "multiple parallel hits hypothesis," whereby multiple factors contribute concurrently to disease pathogenesis has led to advances in the elucidation of hepatic and systemic molecular mechanisms driving NASH and the subsequent NASH-HCC progression; the results are not only extensive but promising for therapeutics. Here, we have summarized the myriad landmark discoveries of recent research into the pathogenic processes underlying NASH-HCC development and with the greatest possibility for a new generation of pharmaceutical products for interference and treatment.
| S-EPMC6700399 | biostudies-literature
Project description:Non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) is increasing globally, but its molecular features are not well defined. We aimed to identify unique molecular traits characterizing NASH-HCC compared to other HCC aetiologies. We collected 80 NASH-HCC and 125 NASH samples from 5 institutions. Expression array (n=53 NASH-HCC; n=74 NASH) and whole exome sequencing (n=50 NASH-HCC) data were compared to HCCs of other aetiologies (n=184). Three NASH-HCC mouse models were analysed with RNAseq/expression-array (n=20). ACVR2A was silenced in HCC cells and proliferation assessed by MTT and colony formation assays. Mutational profiling of NASH-HCC tumours revealed TERT-promoter (56%), CTNNB1 (28%), TP53 (18%) and ACVR2A (10%) as the most-frequently mutated genes. ACVR2A mutation rates were higher in NASH-HCC than in other HCC aetiologies (10% versus 3%, p<0.05). In vitro, ACVR2A silencing prompted a significant increase in cell proliferation in HCC cells. We identified a novel mutational signature (MutSig-NASH-HCC) significantly associated with NASH-HCC (16% vs 2% in viral/alcohol-HCC, p=0.03). Tumour mutational burden (TMB) was higher in non-cirrhotic than in cirrhotic NASH-HCCs (1.45 versus 0.94 mutations/Mb; p<0.0017). Compared to other aetiologies of HCC, NASH-HCCs were enriched in bile and fatty acid signalling, oxidative stress and inflammation, and presented a higher fraction of Wnt/TGF-β proliferation subclass tumours (42% versus 26%, p=0.01) and a lower prevalence of the CTNNB1 subclass. Compared to other aetiologies, NASH-HCC showed a significantly higher prevalence of immunosuppressive cancer field. In three murine models of NASH-HCC key features of human NASH-HCC were preserved. NASH-HCCs display unique molecular features including higher rates of ACVR2A mutations and the presence of a newly identified mutational signature.
2021-06-29 | GSE164760 | GEO
Project description:Hepatocellular carcinoma(HCC) is the sixth most common cancer in the world and is usually caused by viral hepatitis (HBV and HCV), alcoholic, and non-alcoholic fatty liver disease(NAFLD). Viral hepatitis accounts for 80% of HCC cases worldwide. In addition, With the increasing incidence of metabolic diseases, NAFLD is now the most common liver disease and a major risk factor for HCC in most developed countries. This review mainly described the specificity and similarity between the pathogenesis of viral hepatitis(HBV and HCV)-induced HCC and NAFLD-induced HCC. In general, viral hepatitis promotes HCC development mainly through specific encoded viral proteins. HBV can also exert its tumor-promoting mechanism by integrating into the host chromosome, while HCV cannot. Viral hepatitis-related HCC and NASH-related HCC differ in terms of genetic factors, and epigenetic modifications (DNA methylation, histone modifications, and microRNA effects). In addition, both of them can lead to HCC progression through abnormal lipid metabolism, persistent inflammatory response, immune and intestinal microbiome dysregulation.
| S-EPMC9520190 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC), the third major cause of cancer mortality, can result from non-alcoholic steatohepatitis (NASH). Due to limited efficacy of drugs approved for HCC and no drug available yet for NASH, identification of new effective treatments is crucial. Here, we investigated whether NV556, a cyclophilin inhibitor derived from sanglifehrins, would decrease the development of NASH and HCC in a preclinical mouse model. For our experiment, male mice were administered streptozotocin to disrupt pancreatic cells and nourished with high-fat diet since 3 weeks of age. Afterward, NV556 or vehicle was orally administered daily for 6 weeks before the 14-week-old time point for the development of NASH, or 10 weeks before the 30-week-old time point for the establishment of HCC. Body weight, blood glucose level, and liver weight were recorded. Moreover, for NASH, livers were histologically examined for inflammation and steatosis. Collagen was measured by Sirius Red staining of hepatic tissues. Systemic cytokine levels in serum were detected by multiplex assays. For HCC, nodules of livers were measured and scored according to a developed system with number and size of nodules as criteria. NV556 significantly decreased collagen deposition (p = 0.0281), but did not alter inflammation, steatosis, body and liver weight, and systemic cytokine production compared to control mice with NASH symptoms. For HCC, NV556 statistically reduced the number (p = 0.0091) and diameter of tumorous nodules (p = 0.0264), along with liver weight (p = 0.0026) of mice.Our study suggests NV556 as a promising candidate for treatment of NASH-derived fibrosis and HCC.
| S-EPMC6775500 | biostudies-literature