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

P16 protein is a cell cycle regulator involved in the genesis of many types of tumors. In order to study the significance and expression of P16 protein in liver tissue of viral hepatitis, 48 patients with viral hepatitis and 7 cases with hepatocarcinoma were investigated by immunohistochemistry. The results showed that the positive rate of P16 protein expressed in the liver tissues of mild (85.0%) and moderate (91.66%) chronic viral hepatitis were significantly higher than that in liver cirrhosis and hepatocarcinoma (P < 0.01, 0.001), this suggest that the expression of P16 plays an important role in the carcinogenesis.
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PMID:[Study on expression of P16 protein in the liver tissue of viral hepatitis]. 1251 87

Fibrolamellar carcinomas have a unique predilection for younger individuals and arise in livers without recognizable liver disease. In contrast to typical hepatocellular carcinomas, fibrolamellar carcinomas show few chromosomal changes and lack mutation in key genes such as TP53 and CTNNB1. Epigenetic instability, manifesting as methylation of important tumor suppressor gene promoters, has not been investigated in fibrolamellar carcinomas. Thus, the methylation status of 11 tumor suppressor gene promoters was investigated using methylation-specific PCR: RASSF1, CDH1, CDKN2B, HPP1, CDKN2A, GSTP1, P16, RARA, FLJ13081, SOCS1, and TP53. Nine fibrolamellar carcinomas were studied including primary tumors (N=5) and metastatic deposits (N=4) along with control groups of typical hepatocellular carcinoma arising in livers with (N=21) and without cirrhosis (N=10). In fibrolamellar carcinomas, RASSF1A and CDH1 (e-cadherin) were the most commonly methylated genes with 80-100% of tumors methylated. However, overall fibrolamellar carcinomas showed low levels of methylation with no differences between fibrolamellar carcinomas and their paired normal livers. However, fibrolamellar carcinomas showed significantly less methylation than hepatocellular carcinomas that arose in the background of viral cirrhosis. Overall, methylation was most strongly linked to viral cirrhosis. In conclusion, fibrolamellar carcinoma shows low levels of methylation. In contrast, higher levels of promoter methylation are associated with hepatocellular carcinomas that arise in the setting of viral induced cirrhosis.
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PMID:Epigenetic instability is rare in fibrolamellar carcinomas but common in viral-associated hepatocellular carcinomas. 1826 82

CpG island methylator phenotype (CIMP) involves the targeting of multiple genes by promoter hypermethylation. Telomerase plays an important role in the development of cellular immortality and oncogenesis. To gain insight into the role of epigenetic aberration of telomerase-related genes in hepatocarcinogenesis, we determined a hypermethylation profile in HCC. We examined the promoter methylation status of 9 genes associated with telomerase activity in 120 HCC, 120 cirrhosis tissues and 10 normal liver tissues by methylation-specific PCR. Assay of telomerase activity was by TRAP-ELISA. The frequency of promoter methylation of each gene was P21 63.3%, P15 42.5%, P16 62.5%, P53 14.2%, RB 32.5%, P27 48.3%, WTI 54.2%, E2F-1 70.8% and P300 65.8% of 120 HCC. Methylation status of P21, P15, P16, WTI and E2F-1 was significantly associated with HCC and nontumor tissues (p < 0.05). CIMP+ was detected in 61.7% (74/120) HCC and 15% (18/120) cirrhosis tissues, no CIMP+ was present in normal liver tissues (p < 0.001). A significant difference between CIMP status and metastasis was been found in HCC (p < 0.001). Results showed that 94.6% (70/74) HCC and 55.6% (10/18) cirrhosis patients with CIMP+ show expression of high telomerase activity than 45.5% (10/22) HCC and 6.25% (1/16) cirrhosis patients with CIMP- (p < 0.001). CIMP lead to high levels of expression of telomerase activity through the simultaneous inactivation of multiple genes associated with telomerase activity by concordant methylation.
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PMID:CpG island methylator phenotype association with upregulated telomerase activity in hepatocellular carcinoma. 1854 60

To investigate whether aberrant hypermethylation in plasma DNA could be used as diagnosis makers for hepatocellular carcinoma (HCC), we performed methylation-specific PCR (MSP) to check the methylation status of five tumor associated genes in 36 cases of tissue and 42 cases of plasma samples from HCC and liver cirrhosis patients, respectively. The hypermethylation frequency of GSTP1 and RASSF1A showed significant difference between HCCs and liver cirrhosis with or without HBV infection (P<0.05), but differences of the hypermethylation status of APC, E-cadherin, and P16 were not statistically significant. There were no significant differences in the hypermethylation status of five genes between the groups of cirrhosis with and without HBV infection. The significant differences of E-cadherin, GSTP1, P16, and RASSF1A in methylation between HCCs and liver cirrhosis were not observed in the plasma samples. Furthermore, the inconsistent results of MSP and real-time quantitative PCR for the paired samples of tissue and plasma suggested that plasma DNA could not fully stand for tissue DNA. In conclusion, hypermethylation of some specific, but not all, tumor associated genes may be involved in hepatocarcinogenesis; examination of the methylation status of E-cadherin, GSTP1, P16, and RASSF1A in the plasma samples might have limited usage for HCC diagnosis.
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PMID:Methylation of tumor associated genes in tissue and plasma samples from liver disease patients. 1869 70

Hepatocellular carcinoma (HCC) is one of the most common cancers around the globe and third most fatal malignancy. Chronic liver disorders such as chronic hepatitis and liver cirrhosis often lead to the development of HCC. Accumulation of genetic and epigenetic alterations are involved in the development of HCC. Genetic research sparked by recent developments in next generation sequencing has identified the frequency of genetic alterations that occur in HCC and has led to the identification of genetic hotspots. Emerging evidence suggests that epigenetic aberrations are strongly associated with the initiation and development of HCC. Various important genes encoding tumor suppressors including P16, RASSF1A, DLC-1, RUNX3 and SOCS-1 are targets of epigenetic dysregulation during the development of HCC. The present review discusses the importance of epigenetic regulations including DNA methylation, histone modification and microRNA mediated regulation of gene expression during tumorigenesis and their use as disease biomarkers. Furthermore, these epigenetic alterations have been discussed in relationship with promising therapeutic perspectives for HCC and related cancers.
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PMID:Epigenetic mechanisms regulating the development of hepatocellular carcinoma and their promise for therapeutics. 2727 56