p16 Methylation was associated with the development, age, hepatic viruses infection of hepatocellular carcinoma, and p16 expression had a poor survival

Lv, Xueyou; Ye, Guoliang; Zhang, Xinjun; Huang, Tao

doi:10.1097/md.0000000000008106

Cited by 23 publications

(22 citation statements)

References 76 publications

(170 reference statements)

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“…cirrhosis) to hepatocellular nodules and HCC, as well as with Huang et al [15] and Chan et al [27] who reported RASSF1A methylation in the blood and tissues of HCC patients. Our results also showed an increasing frequency of p16 PM from NHT to HCC which is in agreement with the earlier studies [28,29]. Hepatitis C -From Infection to Cure Figure 6.…”

Section: Normal Liver N = 13 (%) Chronic Hepatitis (Ch)supporting

confidence: 93%

The Molecular Background Associated with the Progression of Hepatitis C to Hepatocellular Carcinoma

Zekri¹,

Bahnassy²,

Abdellateif³

2018

Hepatitis C - From Infection to Cure

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Hepatocellular carcinoma (HCC) is a major health problem worldwide. The DNA PM of cancer-related genes plays an important role in the development and progression of HCC. The data reported in our studies provide evidence that PM of p73, p14, and O6-MGMT is associated with HCC, whereas PM of the APC gene is more common in chronic hepatitis (CH) cases. Thus, it could be used as a maker for early detection of HCV-induced chronic active hepatitis. A panel of four genes APC, p73, p14, and O6-MGMT independently affected the classification of cases into HCC and CH with accuracy (89.9%), sensitivity (83.9%), and specificity (94.7%). Also, the detection of PM of APC, FHIT, p15, p16, and E-cadherin in peripheral blood of HCV-infected patients is a highly sensitive and specific. Therefore, blood could be used as efficiently as tissue biopsies to assess PM of different genes. This could help in the follow-up of CH patients and early detection of HCC. We did not observe a significant difference in the methylation status according to the virus type HBV versus HCV. So, plasma DNA is a reliable resource for methylation studies in the future, irrespective of the type of hepatitis infection.

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Section: Normal Liver N = 13 (%) Chronic Hepatitis (Ch)supporting

confidence: 93%

The Molecular Background Associated with the Progression of Hepatitis C to Hepatocellular Carcinoma

Zekri¹,

Bahnassy²,

Abdellateif³

2018

Hepatitis C - From Infection to Cure

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show abstract

“…Furthermore, Lv, Ye, Zhang, and Huang (2017) completely in approximately half of the HCCs examined and the proportion of tumors with reduced p16 immunostaining increased according to the histological stage. Although there was no statistical association between the loss of p16 expression and etiologic factors in individuals with HCC (e.g., sex and age), the loss of p16 expression may be a common event during hepatocarcinogenesis, which may imply that an epigenetic change due to extensive CpG methylation was the main cause of inactivation of p16 in HCC.…”

Section: Discussionmentioning

confidence: 94%

The landscape of DNA methylation in hepatocellular carcinoma

Yang

Zhang

et al. 2018

Journal Cellular Physiology

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Better understanding of the relationship between changes in the overall methylation status of hepatocellular carcinoma (HCC) and disease progression will help us find good strategies for the early detection and treatment of HCC patients. The purpose of the study was to study the relations between the methylation status changes in HCC patients and progression of the disease to enable early detection and treatment of HCC patients. First, the DNA methylation data of 50 HCC samples and the surrounding normal samples were extracted and the change pattern of methylation status in the DNA promoter region of HCC samples against that of normal samples was studied. Then, some DNA methylation genes that could accurately identify cancer and cancer-adjacent tissues were identified using the k-top scoring pair method. Also, a prognostic signature that could predict the survival of HCC patients was constructed based on the overall survival time and death information of the early HCC patients. Finally, the obtained prognostic signature was verified. In conclusion, this study described the changes in the methylation spectrum during the development of HCC and identified genes associated with HCC progression and prognosis, which may offer new opportunities for the diagnosis and treatment of HCC.

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“… 37 , 38 P16 gene promoter region methylation represents the most common mechanism of P16 inactivation in HBV-induced human HCC. 39 As several studies demonstrated, the methylation of P16 may participate in the development of HBV-related HCC. 18 , 19 , 21 , 22 However, the negative results indicated that the exact relationship of P16 gene promoter region methylation with HBV-related HCC susceptibility was still inconclusive.…”

Section: Discussionmentioning

confidence: 99%

Association of GSTP1 and P16 promoter methylation with the risk of HBV-related hepatocellular carcinoma: a meta-analysis

Deng

Zhang

et al. 2018

OTT

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BackgroundStudy on the relationship between glutathione-S-transferase Pi 1 (GSTP1) and P16 promoter region methylation and the risk of hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC) has produced inconsistent results.ObjectivesTo assess the correlation between GSTP1 and P16 promoter methylation frequency and HBV-related HCC susceptibility.MethodsAll relevant studies were identified by searching PubMed, Embase, Web of Science, and China National Knowledge Infrastructure literature databases before December, 2017. The OR and the corresponding 95% CI were calculated to investigate the risk of GSTP1 and P16 promoter methylation rate and HBV-related HCC. Sensitivity analysis was performed and publication bias was estimated using the Begg’s and Egger’s test.ResultsOur meta-analysis identified the relationships of GSTP1 (six studies including 213 HBV-related HCC tumor tissues) and P16 (nine studies with 287 HBV-related HCC tumor tissue) promoter methylation with HCC risk. Compared with normal liver tissue and cirrhosis, the pooled ORs of GSTP1 promoter region methylation in HBV-related HCC cancer tissues were 6.05 (95% CI =1.20–30.52) and 5.21 (95% CI =2.19–12.41), respectively. Compared with paracancerous tissue, normal liver tissue, cirrhosis, and chronic hepatitis B as controls, the pooled ORs of P16 promoter region methylation in HBV-related HCC cancer tissues were 7.18 (95% CI =2.31–22.33), 24.89 (95% CI =3.38–183.03), 5.92 (95% CI =1.78–19.68), and 12.12 (95% CI =0.75–196.50).ConclusionIn summary, our meta-analysis found strong associations between GSTP1 and P16 gene promoter methylation and an increased HBV-related HCC susceptibility. Moreover, GSTP1 and P16 methylation in promoter region could obviously increase the risk of HBV-related HCC in patients with cirrhosis, indicating that these would be promising biomarkers for early clinical diagnosis of HBV-related HCC.

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p16 Methylation was associated with the development, age, hepatic viruses infection of hepatocellular carcinoma, and p16 expression had a poor survival

Abstract: Supplemental Digital Content is available in the text

Cited by 23 publications

References 76 publications

The Molecular Background Associated with the Progression of Hepatitis C to Hepatocellular Carcinoma

The Molecular Background Associated with the Progression of Hepatitis C to Hepatocellular Carcinoma

The landscape of DNA methylation in hepatocellular carcinoma

Association of GSTP1 and P16 promoter methylation with the risk of HBV-related hepatocellular carcinoma: a meta-analysis

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