The correlation of hepatitis B virus pre-S mutation with cellular oxidative DNA damage in hepatocellular carcinoma.
OBJECTIVE
Recent research has proposed a role for HBV pre-S mutation in the development of HCC. Although the mechanism is not clear, pre-S mutant-induced endoplasmic reticulum (ER) stress and oxidative DNA damage may participate in this process. Therefore, we investigated the correlation of HBV pre-S mutation with ER stress and cellular oxidative DNA damage in HBV-related HCC patients.


METHODS
Thirty HBV-related HCC patients and 8 control patients were included. HBV DNA was extracted from sera and the HBV S coding region was analyzed by PCR and sequencing. Immunohistochemical staining for 8-oxoG and OGG1 were performed in HCC and non-neoplastic tissues.


RESULTS
Study subjects were categorized into three groups: the pre-S mutant HBV-infected HCC patients (group 1, n=20), wild-type HBV-infected HCC patients (group 2, n=10) and HBV non-infected patients (group 3, n=8). The expression level of 8-oxoG and OGG1 in non-neoplastic tissue was higher in group 1/2 than in group 3; however, there was no significant difference between group 1 and 2. There was no significant difference in 8-oxoG/OGG1 expressions between HCC and non-neoplastic tissues.


CONCLUSIONS
The present study did not support a pathophysiologic role for HBV pre-S mutation, related to ER stress and oxidative DNA damage, in hepatocarcinogenesis.
Gwak
Geum-Youn
GY
Department of Medicine and Digestive Disease Research Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Lee
Dong Ho
DH
Moon
Tae Gun
TG
Choi
Moon Seok
MS
Lee
Joon Hyeok
JH
Koh
Kwang Cheol
KC
Paik
Seung Woon
SW
Park
Cheol Keun
CK
Joh
Jae-Won
JW
Yoo
Byung Chul
BC
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D004249:DNA Damage / Q000235:genetics*; D045647:DNA Glycosylases / Q000378:metabolism; D004721:Endoplasmic Reticulum; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*; D014759:Viral Envelope Proteins / Q000235:genetics*
D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; D014759:Viral Envelope Proteins; C050806:presurface protein 1, hepatitis B surface antigen; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human