A pre-S gene chip to detect pre-S deletions in hepatitis B virus large surface antigen as a predictive marker for hepatoma risk in chronic hepatitis B virus carriers.
BACKGROUND
Chronic hepatitis B virus (HBV) infection is an important cause of hepatocellular carcinoma (HCC) worldwide. The pre-S1 and -S2 mutant large HBV surface antigen (LHBS), in which the pre-S1 and -S2 regions of the LHBS gene are partially deleted, are highly associated with HBV-related HCC.


METHODS
The pre-S region of the LHBS gene in two hundred and one HBV-positive serum samples was PCR-amplified and sequenced. A pre-S oligonucleotide gene chip was developed to efficiently detect pre-S deletions in chronic HBV carriers. Twenty serum samples from chronic HBV carriers were analyzed using the chip.


RESULTS
The pre-S deletion rates were relatively low (7%) in the sera of patients with acute HBV infection. They gradually increased in periods of persistent HBV infection: pre-S mutation rates were 37% in chronic HBV carriers, and as high as 60% in HCC patients. The Pre-S Gene Chip offers a highly sensitive and specific method for pre-S deletion detection and is less expensive and more efficient (turnaround time 3 days) than DNA sequencing analysis.


CONCLUSIONS
The pre-S1/2 mutants may emerge during the long-term persistence of the HBV genome in carriers and facilitate HCC development. Combined detection of pre-S mutations, other markers of HBV replication, and viral titers, offers a reliable predictive method for HCC risks in chronic HBV carriers.
Shen
Fan-Ching
FC
Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan, Taiwan, Republic of China. jin2348257@hotmail.com
Su
Ih-Jen
IJ
Wu
Han-Chieh
HC
Hsieh
Yi-Hsuan
YH
Yao
Wei-Jen
WJ
Young
Kung-Chia
KC
Chang
Tsung-Chuan
TC
Hsieh
Hui-Chuan
HC
Tsai
Han-Ni
HN
Huang
Wenya
W
D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000209:etiology; D004252:DNA Mutational Analysis / Q000295:instrumentation*; D004279:DNA, Viral / Q000097:blood / Q000235:genetics*; D006511:Hepatitis B Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics* / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000097:blood / Q000821:virology*; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000209:etiology; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012306:Risk; D017384:Sequence Deletion; D014759:Viral Envelope Proteins / Q000235:genetics*
D004279:DNA, Viral; D006511:Hepatitis B Antigens; C096362:L protein, hepatitis B virus; D014759:Viral Envelope Proteins