Prevalence of wild-type in NS5A-PKR protein kinase binding domain in HCV-related hepatocellular carcinoma

Maria Stella De Mitri, Giulia Morsica, Romina Cassini, Sabrina Bagaglio, Marco Zoli, Alfredo Alberti, Mauro Bernardi

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background/Aims: Experimental studies have demonstrated that the wild-type PKR-NS5A strain of hepatitis C virus (HCV) may have oncogenic potential through the binding and functional repression of PKR protein kinase. To assess whether the NS5A-PKR-binding domain may be involved in HCV-related liver carcinogenesis, its sequence was analyzed in the sera of 85 patients with hepatocellular carcinoma (HCC) and in 51 patients with chronic active hepatitis (CAH). In 13 HCC cases sequence analysis was also performed in tumor and nontumor liver tissues. Methods: The nucleotide sequences of the PKR-binding domain were inferred by direct sequencing of the amplified HCV products and deduced amino acids were cpmpared with the sequence of HCV-J. Results: A wild-type or single mutated strain which retains PKR-binding activity was found in 88% of HCC and 69% of CAH cases (P = 0.0096). All but three HCC cases showed no divergences in amino acid changes between serum and liver tissues. The wild-type strains were equally distributed between the HCC with or without cirrhosis. Conclusions: The prevalence of the wild-type NS5A-PKR strain is significantly higher in HCC than in CAH. These data suggest that inhibition of PKR activity by HCV might represent a potential mechanism of HCV-related carcinogenesis.

Original languageEnglish
Pages (from-to)116-122
Number of pages7
JournalJournal of Hepatology
Volume36
Issue number1
DOIs
Publication statusPublished - 2002

Fingerprint

Protein Binding
Hepacivirus
Hepatocellular Carcinoma
Chronic Hepatitis
Liver
Carcinogenesis
eIF-2 Kinase
Amino Acids
Serum
Sequence Analysis
Fibrosis
Neoplasms

Keywords

  • Chronic hepatitis
  • Hepatitis C virus
  • Hepatocellular carcinoma
  • Nonstructural 5A
  • PKR protein kinase

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Prevalence of wild-type in NS5A-PKR protein kinase binding domain in HCV-related hepatocellular carcinoma. / De Mitri, Maria Stella; Morsica, Giulia; Cassini, Romina; Bagaglio, Sabrina; Zoli, Marco; Alberti, Alfredo; Bernardi, Mauro.

In: Journal of Hepatology, Vol. 36, No. 1, 2002, p. 116-122.

Research output: Contribution to journalArticle

De Mitri, Maria Stella ; Morsica, Giulia ; Cassini, Romina ; Bagaglio, Sabrina ; Zoli, Marco ; Alberti, Alfredo ; Bernardi, Mauro. / Prevalence of wild-type in NS5A-PKR protein kinase binding domain in HCV-related hepatocellular carcinoma. In: Journal of Hepatology. 2002 ; Vol. 36, No. 1. pp. 116-122.
@article{0765cc68a3374138a54e3836b018ebcd,
title = "Prevalence of wild-type in NS5A-PKR protein kinase binding domain in HCV-related hepatocellular carcinoma",
abstract = "Background/Aims: Experimental studies have demonstrated that the wild-type PKR-NS5A strain of hepatitis C virus (HCV) may have oncogenic potential through the binding and functional repression of PKR protein kinase. To assess whether the NS5A-PKR-binding domain may be involved in HCV-related liver carcinogenesis, its sequence was analyzed in the sera of 85 patients with hepatocellular carcinoma (HCC) and in 51 patients with chronic active hepatitis (CAH). In 13 HCC cases sequence analysis was also performed in tumor and nontumor liver tissues. Methods: The nucleotide sequences of the PKR-binding domain were inferred by direct sequencing of the amplified HCV products and deduced amino acids were cpmpared with the sequence of HCV-J. Results: A wild-type or single mutated strain which retains PKR-binding activity was found in 88{\%} of HCC and 69{\%} of CAH cases (P = 0.0096). All but three HCC cases showed no divergences in amino acid changes between serum and liver tissues. The wild-type strains were equally distributed between the HCC with or without cirrhosis. Conclusions: The prevalence of the wild-type NS5A-PKR strain is significantly higher in HCC than in CAH. These data suggest that inhibition of PKR activity by HCV might represent a potential mechanism of HCV-related carcinogenesis.",
keywords = "Chronic hepatitis, Hepatitis C virus, Hepatocellular carcinoma, Nonstructural 5A, PKR protein kinase",
author = "{De Mitri}, {Maria Stella} and Giulia Morsica and Romina Cassini and Sabrina Bagaglio and Marco Zoli and Alfredo Alberti and Mauro Bernardi",
year = "2002",
doi = "10.1016/S0168-8278(01)00235-5",
language = "English",
volume = "36",
pages = "116--122",
journal = "Journal of Hepatology",
issn = "0168-8278",
publisher = "Elsevier B.V.",
number = "1",

}

TY - JOUR

T1 - Prevalence of wild-type in NS5A-PKR protein kinase binding domain in HCV-related hepatocellular carcinoma

AU - De Mitri, Maria Stella

AU - Morsica, Giulia

AU - Cassini, Romina

AU - Bagaglio, Sabrina

AU - Zoli, Marco

AU - Alberti, Alfredo

AU - Bernardi, Mauro

PY - 2002

Y1 - 2002

N2 - Background/Aims: Experimental studies have demonstrated that the wild-type PKR-NS5A strain of hepatitis C virus (HCV) may have oncogenic potential through the binding and functional repression of PKR protein kinase. To assess whether the NS5A-PKR-binding domain may be involved in HCV-related liver carcinogenesis, its sequence was analyzed in the sera of 85 patients with hepatocellular carcinoma (HCC) and in 51 patients with chronic active hepatitis (CAH). In 13 HCC cases sequence analysis was also performed in tumor and nontumor liver tissues. Methods: The nucleotide sequences of the PKR-binding domain were inferred by direct sequencing of the amplified HCV products and deduced amino acids were cpmpared with the sequence of HCV-J. Results: A wild-type or single mutated strain which retains PKR-binding activity was found in 88% of HCC and 69% of CAH cases (P = 0.0096). All but three HCC cases showed no divergences in amino acid changes between serum and liver tissues. The wild-type strains were equally distributed between the HCC with or without cirrhosis. Conclusions: The prevalence of the wild-type NS5A-PKR strain is significantly higher in HCC than in CAH. These data suggest that inhibition of PKR activity by HCV might represent a potential mechanism of HCV-related carcinogenesis.

AB - Background/Aims: Experimental studies have demonstrated that the wild-type PKR-NS5A strain of hepatitis C virus (HCV) may have oncogenic potential through the binding and functional repression of PKR protein kinase. To assess whether the NS5A-PKR-binding domain may be involved in HCV-related liver carcinogenesis, its sequence was analyzed in the sera of 85 patients with hepatocellular carcinoma (HCC) and in 51 patients with chronic active hepatitis (CAH). In 13 HCC cases sequence analysis was also performed in tumor and nontumor liver tissues. Methods: The nucleotide sequences of the PKR-binding domain were inferred by direct sequencing of the amplified HCV products and deduced amino acids were cpmpared with the sequence of HCV-J. Results: A wild-type or single mutated strain which retains PKR-binding activity was found in 88% of HCC and 69% of CAH cases (P = 0.0096). All but three HCC cases showed no divergences in amino acid changes between serum and liver tissues. The wild-type strains were equally distributed between the HCC with or without cirrhosis. Conclusions: The prevalence of the wild-type NS5A-PKR strain is significantly higher in HCC than in CAH. These data suggest that inhibition of PKR activity by HCV might represent a potential mechanism of HCV-related carcinogenesis.

KW - Chronic hepatitis

KW - Hepatitis C virus

KW - Hepatocellular carcinoma

KW - Nonstructural 5A

KW - PKR protein kinase

UR - http://www.scopus.com/inward/record.url?scp=0036130416&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036130416&partnerID=8YFLogxK

U2 - 10.1016/S0168-8278(01)00235-5

DO - 10.1016/S0168-8278(01)00235-5

M3 - Article

C2 - 11804673

AN - SCOPUS:0036130416

VL - 36

SP - 116

EP - 122

JO - Journal of Hepatology

JF - Journal of Hepatology

SN - 0168-8278

IS - 1

ER -