Skip to main content

ORIGINAL RESEARCH article

Front. Genet.
Sec. Cancer Genetics and Oncogenomics
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1454153

Circle-seq reveals that eccDNA may be a key blood biomarker for HBV-associated liver cancer

Provisionally accepted
Xiao K. Ran Xiao K. Ran 1*Xiao F Zhao Xiao F Zhao 2Zhen W Wei Zhen W Wei 3Hua Z Pang Hua Z Pang 2Yan F Tang Yan F Tang 2Rong Liu Rong Liu 2Tie X Wu Tie X Wu 1Xu D Liu Xu D Liu 2
  • 1 Guangxi University of Chinese Medicine, Nanning, China
  • 2 Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi Zhuang Region, China
  • 3 Nanning No.4 People's Hospital, Nanning, China

The final, formatted version of the article will be published soon.

    Introduction: Extrachromosomal circular DNA (eccDNA) regulates tumor occurrence and development. Relevant eccDNA profiles have been established for various types of cancer; however, the eccDNA expression profiles in the blood of patients with hepatocellular carcinoma (HCC) and liver cirrhosis (LC) remain unknown. The present study aimed to investigate the eccDNA expression profiles in the blood of patients with HCC and LC.Methods: Circle-seq was used to detect eccDNAs in the blood samples. Full transcript sequencing was used to analyze the RNA in the samples. Geno Ontology enrichment and Kyoto Encyclopedia of Genes and Genome pathway analyses were performed on differentially expressed eccDNA-related genes. The identified eccDNA is combined with mRNA to screen target genes using bioinformatics analysis. EccDNAs were confirmed through polymerase chain reaction and Sanger sequencing.Results: Overall, 103235 eccDNAs were identified in HCC, whereas 67110 eccDNAs were detected in LC. In total, 7095 upregulated eccDNAs and 1284 downregulated eccDNAs were identified.Following analysis of differential genes using bioinformatics, six candidate genes were screened out based on gene expression and cancer relevance. Experiments have verified that LAMA4 [circle112550019- 112550510] and KANK1 [circle674459-674907] are real and expressed target genes, and their source genes are closely related to the survival time of patients with liver cancer.Our research results revealed the main characteristics of eccDNAs in the blood of patients with HBV-related HCC and LC. It was found that eccDNAs were mainly less than 1000 bp in length. Difference analysis showed that some eccDNAs had consistent and overlapping expressions with mRNAs. We found that LAMA4 [circle112550019-112550510] and KANK1 [circle674459-674907] are target genes related to HCC, and both of them may become potential biomarkers for the diagnosis and prognosis of HCC.

    Keywords: biomarkers, Expression profiles, Target genes, Whole transcriptome sequencing, Extrachromosomal circular DNA, Hepatocellular Carcinoma, Liver Cirrhosis

    Received: 24 Jun 2024; Accepted: 23 Dec 2024.

    Copyright: © 2024 Ran, Zhao, Wei, Pang, Tang, Liu, Wu and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Xiao K. Ran, Guangxi University of Chinese Medicine, Nanning, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.