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

IntroductionExtrachromosomal 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) rem...

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Main Authors: Xiao K. Ran, Xiao F. Zhao, Zhen W. Wei, Hua Z. Pang, Yan F. Tang, Rong Liu, Tie X. Wu, Xu D. Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Genetics
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Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2024.1454153/full
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author Xiao K. Ran
Xiao F. Zhao
Zhen W. Wei
Hua Z. Pang
Yan F. Tang
Rong Liu
Tie X. Wu
Xu D. Liu
author_facet Xiao K. Ran
Xiao F. Zhao
Zhen W. Wei
Hua Z. Pang
Yan F. Tang
Rong Liu
Tie X. Wu
Xu D. Liu
author_sort Xiao K. Ran
collection DOAJ
description IntroductionExtrachromosomal 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.MethodsCircle-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.ResultsOverall, 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.ConclusionOur 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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publisher Frontiers Media S.A.
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spelling doaj-art-5a60d9badd3e403db5363835dad412b72025-01-09T06:10:52ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-01-011510.3389/fgene.2024.14541531454153Circle-seq reveals that eccDNA may be a key blood biomarker for HBV-associated liver cancerXiao K. Ran0Xiao F. Zhao1Zhen W. Wei2Hua Z. Pang3Yan F. Tang4Rong Liu5Tie X. Wu6Xu D. Liu7Graduate School, Guangxi University of Chinese Medicine, Nanning, ChinaHepatology Department, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, ChinaHepatology Department, Nanning Fourth People’s Hospital, Nanning, ChinaHepatology Department, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, ChinaHepatology Department, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, ChinaHepatology Department, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, ChinaGraduate School, Guangxi University of Chinese Medicine, Nanning, ChinaHepatology Department, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, ChinaIntroductionExtrachromosomal 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.MethodsCircle-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.ResultsOverall, 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.ConclusionOur 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.https://www.frontiersin.org/articles/10.3389/fgene.2024.1454153/fullbiomarkersexpression profilestarget geneswhole transcriptome sequencingextrachromosomal circular DNAhepatocellular carcinoma
spellingShingle Xiao K. Ran
Xiao F. Zhao
Zhen W. Wei
Hua Z. Pang
Yan F. Tang
Rong Liu
Tie X. Wu
Xu D. Liu
Circle-seq reveals that eccDNA may be a key blood biomarker for HBV-associated liver cancer
Frontiers in Genetics
biomarkers
expression profiles
target genes
whole transcriptome sequencing
extrachromosomal circular DNA
hepatocellular carcinoma
title Circle-seq reveals that eccDNA may be a key blood biomarker for HBV-associated liver cancer
title_full Circle-seq reveals that eccDNA may be a key blood biomarker for HBV-associated liver cancer
title_fullStr Circle-seq reveals that eccDNA may be a key blood biomarker for HBV-associated liver cancer
title_full_unstemmed Circle-seq reveals that eccDNA may be a key blood biomarker for HBV-associated liver cancer
title_short Circle-seq reveals that eccDNA may be a key blood biomarker for HBV-associated liver cancer
title_sort circle seq reveals that eccdna may be a key blood biomarker for hbv associated liver cancer
topic biomarkers
expression profiles
target genes
whole transcriptome sequencing
extrachromosomal circular DNA
hepatocellular carcinoma
url https://www.frontiersin.org/articles/10.3389/fgene.2024.1454153/full
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