Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NS5A and E2 proteins of the hepatitis C virus (HCV) have the potential to repress protein kinase R (PKR) that exerts a tumour suppressor function. We investigated the relationship between amino acid variations in the NS5A-PKR-binding domain and E2-PKR-eIF2alpha phosphorylation homology domain (PePHD) region and the development of hepatocellular carcinoma (HCC) in chronic HCV-1b patients. In a cross-sectional, hospital-based setting, we compared the amino acid sequences of NS5A-PKR-binding domain and E2-PePHD in the sera of 104 chronic hepatitis, 44 cirrhosis and 96 HCC patients. The nucleotide sequences were inferred by direct sequencing of the amplified HCV products and deduced amino acid were compared with the sequence of HCV-J. By univariate analysis, old age, lower viral load, fewer amino acid substitutions in the NS5A-PKR-binding domain (codons 2209-2274) and the interferon sensitivity-determining region (ISDR; codons 2209-2248), and wild-type amino acid at codon 2209 and codon 2240 was significantly correlated with HCC, whereas substitutions in the E2-PePHD was not. Patients with a mutated-type (> or = 4) NS5A-ISDR had a lower prevalence of HCC than those with intermediate or wild type (P < 0.05). Based on stepwise logistic regression analysis, age [odds ratio (OR): 1.132, P < 0.001], viral load (OR: 0.305, P < 0.001) and mutated-type ISDR (OR: 0.137, P = 0.001) were independently associated with HCC. In conclusion, NS5A-ISDR variations may play an important role in the development of HCV-related HCC.
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PMID:Association of amino acid variations in the NS5A and E2-PePHD region of hepatitis C virus 1b with hepatocellular carcinoma. 1808 46

Hepatocellular carcinoma is related to various etiologies including hepatitis B, hepatitis C, high alcohol intake, aflatoxin B1 and metabolic syndrome. Most of the time HCC developed on cirrhosis. Consequently, the mechanisms of carcinogenesis of these different risk factors are difficult to separate from the events leading to cirrhosis. In contrast, aflatoxin B1 and hepatitis B have a clear direct oncogenic role through point mutations in the TP53 tumour suppressor gene and insertional mutagenesis respectively. Finally, next-generation sequencing and transcriptome analysis will refine our knowledge of the relationship between aetiology and the genetic events that draw the mutational landscape of hepatocellular carcinoma.
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PMID:Pathogenesis of hepatocellular carcinoma according to aetiology. 2526 Mar 19

Background: HCV infection is related to aberrant methylation of several genes. RASSF1A, E-Cadherin and RUNX3 are tumour suppressor genes that may be inactivated by hypermethylation in many tumours including hepatocellular carcinoma (HCC). We hypothesized that methylation is a diagnostic biomarker for HCC in patients with HCV-related liver cirrhosis.Methods: We recruited 207 cases of HCV-related liver cirrhosis, 193 HCC patients and 53 healthy controls. Methylation-specific polymerase chain reaction for detection of circulating hypermethylated RASSF1A, E-Cadherinand RUNX3. Alpha fetoprotein (AFP) was measured by commercial immunoassay.Results: Significant hypermethylation of the three genes was found in the HCC group compared to both cirrhosis and healthy groups (P < 0.001), whereas no significant difference in hypermethylation was found between cirrhosis and healthy groups (P = 0.17, 0.50 and 0.14, respectively). No significant links were found between hypermethylated RASSF1A, E-Cadherin and RUNX3 and stages of Barcelona Clinic of Liver Cancer score (P =0.21, 0.63 and 0.98, respectively). No significant associations were found between AFP value and hypermethylated genes in cirrhosis and HCC groups (P = 0.82) except with E-Cadherin in HCC (P = 0.02). In multiple regression analysis, RASSF1A and E-Cadherin were predictors of HCC within cirrhosis cases, but only E-Cadherin was an independent risk factor for prediction of HCC in cases with low AFP (P = 0.01).Conclusions: The presence of hypermethylated serum RASSF1A, E-Cadherin and RUNX3 is linked to HCC in patients with HCV-related cirrhosis. Only E-Cadherin is an independent risk factor for prediction of HCC with low AFP. These findings may be of diagnostic value.
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PMID:Methylation of tumour suppressor genes RUNX3, RASSF1A and E-Cadherin in HCV-related liver cirrhosis and hepatocellular carcinoma. 3179 Mar 42

Liver cancer (hepatocellular carcinoma, HCC) is one of the most prevalent cancers worldwide. Several etiological factors of HCC, including hepatitis B or hepatitis C virus infection, liver cirrhosis and aflatoxin B1 intake has been identified. HBx, which is an oncogenic protein encoded by the hepatitis B virus, is strongly associated with hepatocarcinogenesis. Using stable HBx-expressing cell, we showed that HBx induced chromosome gain, with amplification of centrosomes numbers and deregulation of centrosome ultrastructure. To dissect the mechanism for chromosome instability, our result revealed that HBx contributed to a hyperactive centrosome-microtubule dynamics by accelerating microtubule nucleation and polymerization. Further investigations suggested that HBx interacted with a centrosome linker protein TAX1BP2, which has previously been shown to function as an intrinsic block of centrosome amplification and a tumour suppressor in HCC. Restoring TAX1BP2 was able to block HBx-mediated centrosome amplification and abolish the HBx-mediated centrosome aberration, thereby suppressing chromosome instability. Thus, we demonstrate here a mechanism by which HBx deregulates centrosome-microtubule dynamics through interacting with TAX1BP2, which underlines the possibility of restoration of TAX1BP2 to rescue cells from chromosome instability.
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PMID:Centrosomal protein TAX1BP2 inhibits centrosome-microtubules aberrations induced by hepatitis B virus X oncoprotein. 3282 1


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