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Chinese Journal of Digestion and Medical Imageology(Electronic Edition) ›› 2021, Vol. 11 ›› Issue (04): 152-157. doi: 10.3877/cma.j.issn.2095-2015.2021.04.003

• Clinical Science Research • Previous Articles     Next Articles

Characterization of hepatitis B virus DNA integration pattern in liver cancer based on bioinformatics analysis

Xiaoli Xi1, Bilan Yang1, Junchao Dong2, Bin Wu1, Yidong Yang1,()   

  1. 1. Department of Gastroenterology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
    2. Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
  • Received:2021-02-02 Online:2021-08-01 Published:2021-08-18
  • Contact: Yidong Yang

Abstract:

Objective

To investigate the characteristics of hepatitis B virus (HBV) DNA integration in liver cancer.

Methods

Combined with the sequencing results of cancer tissues and adjacent tissues of liver cancer patients in previous studies, the HBV DNA integration sites were summarized, and the distribution of HBV DNA integration sites in liver cancer tissues and adjacent tissues at chromosome level, repetitive sequence level and gene level was analyzed by bioinformatics method. The relationship between integration and transcriptional activity was explored by calculating the distance between integration sites and transcriptional active sites identified by Bedtools software, and the differences of this feature in liver cancer tissues, adjacent tissues, hotspot genome and non-hotspot genome.

Results

HBV DNA integration was found in both liver cancer tissues and adjacent tissues, and the integration sites showed dominant integration at chromosome level, repetitive sequence level, and gene level. In cancer tissues and adjacent tissues, 8.5% and 9.0% of HBV integration sites were located in transcriptional active regions, while only 3.4% of HBV integration sites in random sequences were found. According to Poisson distribution, the hotspot genes were identified in HBV DNA integrated genes in liver cancer tissues. In liver cancer tissues, more HBV DNA was integrated into high transcriptional activity regions in the hotspot genomes than in the non-hotspot genomes (16.5% vs 3.0%, P<0.001).

Conclusion

The integration characteristics of HBV DNA in liver cancer tissues and adjacent tissues are not identical, but in both liver cancer tissues and adjacent tissues, HBV DNA tends to integrate into high transcriptional activity region.

Key words: Liver cancer, Hepatitis B virus, DNA, Integration

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