Frontiers in Microbiology (Apr 2022)

Hepatitis B Virus Pregenomic RNA Reflecting Viral Replication in Distal Non-tumor Tissues as a Determinant of the Stemness and Recurrence of Hepatocellular Carcinoma

  • Yiwei Xiao,
  • Junning Cao,
  • Ze Zhang,
  • Chaoting Zeng,
  • Guomin Ou,
  • Jihang Shi,
  • Zhixiu Liu,
  • Zhixiu Liu,
  • Yi Li,
  • Juan Deng,
  • Yinzhe Xu,
  • Wenwen Zhang,
  • Jie Li,
  • Tong Li,
  • Tong Li,
  • Hui Zhuang,
  • Hui Zhuang,
  • Shichun Lu,
  • Kuanhui Xiang,
  • Kuanhui Xiang

DOI
https://doi.org/10.3389/fmicb.2022.830741
Journal volume & issue
Vol. 13

Abstract

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BackgroundThe existence of hepatic cancer stem cells (CSCs) contributes to chemotherapy resistance and cancer recurrence after treatment or surgery. However, very little is known about the hepatitis B virus (HBV) replication and its relationship with the stemness of hepatocellular carcinoma (HCC) in HBV-related HCC patients.MethodsWe collected tumor tissues (T), matched adjacent non-tumor tissues (NT), and distal non-tumor tissues (FNT) from 55 HCC patients for analysis.ResultsWe found HBV DNA levels were higher in T samples than NT and FNT samples, but HBV pgRNA and total RNA expressed lower in T samples. HBV pgRNA and total RNA correlate to HBV DNA among the T, NT, and FNT samples. Further evidence for HBV replication in T samples was provided by HBV S, reverse transcriptase, and X genes sequencing, showing that HBV sequences and genotypes differed between T and matched NT and FNT samples. HBV pgRNA and total RNA showed more frequent significant correlations with CSC markers in NT samples in HBsAg-positive patients. The markers CD133 and OCT4 expressed higher in FNT samples, and HBV replication marker of pgRNA levels was significantly positively correlated to these two markers only in FNT samples. The detection of pgRNA and OCT4 in FNT was correlated to the recurrence of HCC in the resection of HCC patients. Analysis of HBV receptor, sodium taurocholate co-transporting polypeptide (NTCP), showed that NTCP was correlated negatively to CSC markers in T samples, except for the CD44.ConclusionHBV replication may present in HCC with a weak transcriptomic signature. Moreover, the expression level of HBV pgRNA in distal non-tumor tissues is a sensitive marker for HBV replication and prognosis, which is associated with CSC-related markers especially with OCT4 in distal non-tumor tissues and recurrence of HCC in HBV-related HCC patients.

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