Epstein-Barr virus in hepatocellular carcinogenesis

Abstract

AIM:In recent years, studies have suggested that EpsteinBarr virus (EBV) is associated with HCC. The present study was to determine the prevalence of EBV in HCC patients, and whether EBV acted synergistically with hepatitis viruses in HCC carcinogenesis. METHODS:Liver tissue 115 HCC patients and 26 noncarcinoma patients were studied. Polymerase chain reaction (PCR) was performed to detect EBV BamHI W DNA, EBV LMP1 DNA, HBV X DNA, and HBV S DNA. Reverse transcription PCR (RT-PCR) was performed to detect HCV RNA and HDV RNA. Immunohistochemistry was performed to detect LMP1, HBsAg, HBcAg and HCV. The positive ratios were compared between HCC group and control group by χ 2 test. RESULTS:Totally, 78 HCC samples whose β-globulin DNA was positively detected by amplified PCR were selected. PCR was performed in all cases for EBV DNA and HBV DNA.RT-PCR was performed in 18 cases for HCV RNA and HDV RNA. EBV BamHI W and EBV LMP1 were positive in 18 and 6 cases, respectively. HBV X gene and HBV S gene were positive in 42 and 27 cases respectively. HCV was positive in one of the 18 cases, and none was positive for HDV. The positive rates were 28.2% (22 of 78) for EBV DNA (BamHI W and/or LMP1) and 56.4% (44 of 78) for HBV DNA (X gene and/or S gene) respectively. In addition, 12 cases were positive for both EBV DNA and HBV DNA. Among the 26 cases in the control group, 2 cases were positive for EBV BamHI W, 4 positive for HBV X gene and 3 positive for HBV S gene. The positive rates were 8.0% (2 of 26) and 23.1% (6 of 26), respectively, for EBV DNA and HBV DNA. The result of DNA sequencing of BamHI W was 100% homologous with the corresponding sequence of B95-8. There was significant difference in EBV infection rate between HCC patients and controls (χ 2 = 4.622, P<0.05). The difference in HBV infection rate was also significant (χ 2 = 8.681, P<0.05). However, there was no obvious correlation between HBV and EBV in HCC patients (χ 2 = 0.835, P>0.05). LMP1, HBV (HBsAg, HBcAg) and HCV were detected positively in 25, 45 and 6 of 78 cases of HCC tissues respectively. In the 26 control cases, the corresponding positive cases were 2, 4 and 0. The difference in EBV infection rate between HCC patients and control cases was statistically significant (χ 2 = 6.02, P<0.05). The difference in HBV infection rate was also statistically significant (χ 2 = 10.03, P<0.05). In the 25 cases with positive LMP1 expression, 6 were in the nuclei of tumor cells, 9 in the cytoplasm of tumor cells and 10 in mesenchymal lymphocyte cytoplasm. CONCLUSION:The existence of EBV infection in HCC tissues suggests that EBV may be involved in the hepatocellular carcinogenesis in China. HBV infection may be a major cause of HCC. There is no correlation between EBV and HBV in the development of HCC. The prevalence of HCV infection is low in our area, and HDV appears not to play a direct role in hepatocellular carcinogenesis.

Epstein-Barr virus (EBV) and its associated human cancers - Genetics, epigenetics, pathobiology and novel therapeutics

“…Western blotting and RT-PCR also demonstrated the expression of EBNA1 (from Qp) and BARTs, but not EBERs, LMP1, LMP2 or BZLF1. Recently, a small proportion of Chinese hepatocellular carcinomas have also been shown to be EBV positive (451). However, more studies of European and American HCC have yielded negative results, indicating a possible ethnic difference in the association (452)(453)(454).…”

BamHI‐A rightward frame 1, an Epstein–Barr virus‐encoded oncogene and immune modulator

“…EBV-linked GC is considered a distinct disease entity compared with Helicobacter pylori -associated GC. EBV has been associated with breast cancer 20 , 21 and hepatocellular carcinoma 22 , 23 , but supporting evidence is limited or contrary 24 , 25 .…”

De novo hepatocellular carcinoma post‐multivisceral transplantation in a child

“…HCV and HBV serologies were repeatedly checked and were also negative in the child; therefore, viral hepatitis did not play a role. She had recurrent EBV; however, EBV increases risk of HCC only in the presence of HCV and has not been found to have an association on its own . The patient was not exposed to hepatocarcinogens, and there was no evidence of cirrhosis in this patient.…”