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

IF 2.8 3区生物学 Q2 GENETICS & HEREDITY Frontiers in Genetics Pub Date : 2025-01-09 eCollection Date: 2024-01-01 DOI:10.3389/fgene.2024.1454153

Xiao K Ran, Xiao F Zhao, Zhen W Wei, Hua Z Pang, Yan F Tang, Rong Liu, Tie X Wu, Xu D Liu

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Abstract

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, 103,235 eccDNAs were identified in HCC, whereas 67,110 eccDNAs were detected in LC. In total, 7,095 upregulated eccDNAs and 1,284 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.

Conclusion: 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 1,000 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.

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Circle-seq显示，ecdna可能是hbv相关肝癌的关键血液生物标志物。

简介：染色体外环状DNA调控肿瘤的发生发展。已经建立了各种类型癌症的相关ecdna谱；然而，eccDNA在肝细胞癌（HCC）和肝硬化（LC）患者血液中的表达谱尚不清楚。本研究旨在探讨HCC和LC患者血液中eccDNA的表达谱。方法：采用Circle-seq法检测血样中eccdna。采用全转录序列法分析样品中的RNA。对差异表达的eccdna相关基因进行了Geno Ontology富集、京都基因百科全书和基因组通路分析。将鉴定的eccDNA与mRNA结合，利用生物信息学分析筛选靶基因。eccdna经聚合酶链反应和Sanger测序证实。结果：总体而言，在HCC中检测到103235个eccdna，而在LC中检测到67110个eccdna。总共鉴定出7095个上调的eccdna和1284个下调的eccdna。利用生物信息学对差异基因进行分析后，根据基因表达和癌症相关性筛选出6个候选基因。实验证实LAMA4 [circle112550019-112550510]和KANK1 [circle674459-674907]是真实表达的靶基因，其源基因与肝癌患者的生存时间密切相关。结论：我们的研究结果揭示了hbv相关性HCC和LC患者血液中eccdna的主要特征。结果发现，eccdna的长度主要小于1000 bp。差异分析显示，部分eccdna与mrna表达一致或重叠。我们发现LAMA4 [circle112550019-112550510]和KANK1 [circle674459-674907]是与HCC相关的靶基因，两者都可能成为HCC诊断和预后的潜在生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Genetics Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

5.50

自引率

8.10%

发文量

3491

审稿时长

14 weeks

期刊介绍： Frontiers in Genetics publishes rigorously peer-reviewed research on genes and genomes relating to all the domains of life, from humans to plants to livestock and other model organisms. Led by an outstanding Editorial Board of the world’s leading experts, this multidisciplinary, open-access journal is at the forefront of communicating cutting-edge research to researchers, academics, clinicians, policy makers and the public. The study of inheritance and the impact of the genome on various biological processes is well documented. However, the majority of discoveries are still to come. A new era is seeing major developments in the function and variability of the genome, the use of genetic and genomic tools and the analysis of the genetic basis of various biological phenomena.