title: Variation of hepatitis C virus load, hypervariable region 1 quasispecies and CD81 hepatocyte expression in hepatocellular carcinoma and adjacent non-cancerous liver.
abstract: Hepatitis C virus (HCV) infection is etiologically associated with the development of hepatocellular carcinoma (HCC) worldwide. HCV has been reported to exist and replicate in both HCC and adjacent non-cancerous liver tissue, but limited information was available on HCV viral load and quasispecies composition in HCC relative to adjacent non-cancerous hepatocytes. Previous study has also suggested CD81, a surface hepatocyte protein, as a receptor for HCV. To clarify the above, HCV-RNA and CD81-RNA titers in 20 paired hepatectomized liver and serum were quantitatively measured by chemiluminescent RT-cPCR. Hypervariable region 1 (HVR-1) variations of parallel specimens were analyzed after subcloning in 6 patients. HCV-RNA levels in serum and non-cancerous liver were markedly higher for HCV genotype 1 than genotype non-1. HCV levels were markedly higher in non-cancerous liver than in HCC (P = 0.001) in a genotype-independent manner, with a mean ratio of 56:1 for non-cancerous tissue to HCC. Both non-cancerous and HCC tissues had the same level of CD81-RNA expression, which was not linked to HCV load. HCV-RNA quantity in both HCC and non-cancerous liver correlated with the number of HVR-1 quasispecies in the tissue, and distinct HVR-1 subclones existed.
authors.affiliation: Departments of Medical Technology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China. t7908077@mail.ncku.edu.tw
authors.forename: Kung-Chia
authors.initials: KC
authors.lastname: Young
authors.forename: Pin-Wen
authors.initials: PW
authors.lastname: Lin
authors.forename: Wei-Chiang
authors.initials: WC
authors.lastname: Hsiao
authors.forename: Ting-Tsung
authors.initials: TT
authors.lastname: Chang
authors.forename: Yu-Chung
authors.initials: YC
authors.lastname: Chang
authors.forename: Hwa-Lin
authors.initials: HL
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000235:genetics*; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification*; D022781:Hepatocytes / Q000276:immunology* / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D008969:Molecular Sequence Data; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000097:blood / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D060225:Tetraspanin 28; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D015703:Antigens, CD; C554798:CD81 protein, human; D004279:DNA, Viral; C400562:HVR1 protein, Hepatitis C virus; D008565:Membrane Proteins; D012367:RNA, Viral; D011991:Receptors, Virus; D060225:Tetraspanin 28; D014764:Viral Proteins; D012313:RNA