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Association of p16INK4A hypermethylation with hepatitis B virus X protein expression in the early stage of HBV-associated hepatocarcinogenesis.
Pathol Int. 2007 Jun; 57(6):328-36.PI

Abstract

The aim of the present study was to explore the relationship between methylation status of the p16(INK4A) promoter and some HBV-related factors, and the role of these factors in p16(INK4A) hypermethylation and hepatocellular carcinoma (HCC) progression. Twenty-three cases of surgically resected HBV-associated HCC and 25 fine-needle aspiration biopsy cases of chronic hepatitis B (CHB) were studied. The methylation status of the p16(INK4A) promoter was determined by methylation-specific polymerase chain reaction (PCR). Two-step immunohistochemical staining showed the expression of viral antigens in situ. Tissue HBV-DNA levels were determined by fluorescence quantitative real-time PCR. PCR and the direct sequencing method were used for mutation analysis. In peritumoral tissues (P = 0.025) and CHB samples (P = 0.029), the expression of hepatitis B virus X protein (HBx) was higher in methylated groups of p16(INK4A) promoter than in unmethylated groups. Other HBV factors including hepatitis B surface antigen and hepatitis B core antigen, tissue HBV-DNA levels and HBV x gene mutations had no relation to the methylation status of p16(INK4A) promoter. The data indicate that p16(INK4A) promoter hypermethylation correlated closely with higher HBx expression in the precancerous lesions, suggesting that HBx may play an important role in the early stage of HBV-associated hepatocarcinogenesis via induction of hypermethylation of p16(INK4A) promoter.

Authors+Show Affiliations

Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17539963

Citation

Zhu, Rong, et al. "Association of p16INK4A Hypermethylation With Hepatitis B Virus X Protein Expression in the Early Stage of HBV-associated Hepatocarcinogenesis." Pathology International, vol. 57, no. 6, 2007, pp. 328-36.
Zhu R, Li BZ, Li H, et al. Association of p16INK4A hypermethylation with hepatitis B virus X protein expression in the early stage of HBV-associated hepatocarcinogenesis. Pathol Int. 2007;57(6):328-36.
Zhu, R., Li, B. Z., Li, H., Ling, Y. Q., Hu, X. Q., Zhai, W. R., & Zhu, H. G. (2007). Association of p16INK4A hypermethylation with hepatitis B virus X protein expression in the early stage of HBV-associated hepatocarcinogenesis. Pathology International, 57(6), 328-36.
Zhu R, et al. Association of p16INK4A Hypermethylation With Hepatitis B Virus X Protein Expression in the Early Stage of HBV-associated Hepatocarcinogenesis. Pathol Int. 2007;57(6):328-36. PubMed PMID: 17539963.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of p16INK4A hypermethylation with hepatitis B virus X protein expression in the early stage of HBV-associated hepatocarcinogenesis. AU - Zhu,Rong, AU - Li,Bai-Zhou, AU - Li,Hua, AU - Ling,Yu-Qin, AU - Hu,Xi-Qi, AU - Zhai,Wei-Rong, AU - Zhu,Hong-Guang, PY - 2007/6/2/pubmed PY - 2007/7/26/medline PY - 2007/6/2/entrez SP - 328 EP - 36 JF - Pathology international JO - Pathol. Int. VL - 57 IS - 6 N2 - The aim of the present study was to explore the relationship between methylation status of the p16(INK4A) promoter and some HBV-related factors, and the role of these factors in p16(INK4A) hypermethylation and hepatocellular carcinoma (HCC) progression. Twenty-three cases of surgically resected HBV-associated HCC and 25 fine-needle aspiration biopsy cases of chronic hepatitis B (CHB) were studied. The methylation status of the p16(INK4A) promoter was determined by methylation-specific polymerase chain reaction (PCR). Two-step immunohistochemical staining showed the expression of viral antigens in situ. Tissue HBV-DNA levels were determined by fluorescence quantitative real-time PCR. PCR and the direct sequencing method were used for mutation analysis. In peritumoral tissues (P = 0.025) and CHB samples (P = 0.029), the expression of hepatitis B virus X protein (HBx) was higher in methylated groups of p16(INK4A) promoter than in unmethylated groups. Other HBV factors including hepatitis B surface antigen and hepatitis B core antigen, tissue HBV-DNA levels and HBV x gene mutations had no relation to the methylation status of p16(INK4A) promoter. The data indicate that p16(INK4A) promoter hypermethylation correlated closely with higher HBx expression in the precancerous lesions, suggesting that HBx may play an important role in the early stage of HBV-associated hepatocarcinogenesis via induction of hypermethylation of p16(INK4A) promoter. SN - 1320-5463 UR - https://www.unboundmedicine.com/medline/citation/17539963/Association_of_p16INK4A_hypermethylation_with_hepatitis_B_virus_X_protein_expression_in_the_early_stage_of_HBV_associated_hepatocarcinogenesis_ L2 - https://doi.org/10.1111/j.1440-1827.2007.02104.x DB - PRIME DP - Unbound Medicine ER -