Objective The present study aims to compare genetic variation of HBV genome S region and quasispecies charac-teristics originated tumor tissues(TT)and adjacent non-tumor tissues(ANTT)of HCC patients using next generation sequencing(NGS)method.Methods Thirty-nine HBV-related HCC patients were included in this study.Paired samples of TT and ANTT were collected and massively parallel sequencing were conducted on HBV genome S region after HBV DNA extraction.S region from patients samples were aligned with S region reference sequence of HBV genotype C and mutation ratio were compared among sample origination.Gene complexity of nucleotide acid and amino acid were calculated and compared between different sample groups.NGS data of S region from different sample types were compared by sequence signature based method and principal coor-dinate analysis(PCoA)were carried out.Distribution of mutations belong to different levels of occurrence frequence in MHR and α-determinant were compared between TT and ANTT samples.Results The level of cccDNA in TT group was significantly higher than that in paired ANTT group.Both in nucleotide acid and amino acid levels,the complexity of S region in ANTT samples were higher than in TT.Specifically,amino acid sites contributing to the immune escape,such as T131N,G145R,occurred more fre-quently in TT(P<0.001).Conclusion There were significantly difference in HBV S region between HCC TT and ANTT.HBV quasispecies had a lower genome complexity and diversity tumor cells.Based on our research,we can speculate that a distinct HBV evolution was conditioned by the differential host cellular environment of tumor and non-tumor following HCC development.
关键词
乙型肝炎病毒/肝细胞癌/二代测序/变异/肿瘤组织
Key words
Hepatitis B virus/Hepatocellular carcinoma/Next Generation Sequencing/variation/Tumor tissues
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