赣南医学院学报2024,Vol.44Issue(7) :659-665.DOI:10.3969/j.issn.1001-5779.2024.07.001

肾透明细胞癌患者血浆染色体外环状DNA分子特征的研究

Characterization of extrachromosomal circular DNAs in plasma of patients with clear cell renal cell carcinoma

李清 张睿轩 杨晶晶 黄后宝 冯钢
赣南医学院学报2024,Vol.44Issue(7) :659-665.DOI:10.3969/j.issn.1001-5779.2024.07.001

肾透明细胞癌患者血浆染色体外环状DNA分子特征的研究

Characterization of extrachromosomal circular DNAs in plasma of patients with clear cell renal cell carcinoma

李清 1张睿轩 1杨晶晶 1黄后宝 2冯钢1
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作者信息

  • 1. 皖南医学院第一附属医院检验科
  • 2. 皖南医学院第一附属医院泌尿外科,安徽 芜湖 241001
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摘要

目的:探讨肾透明细胞癌(Clear cell renal cell carcinoma,ccRCC)患者血浆染色体外环状DNA(Extrachromosomal circular DNA,eccDNAs)的分子特征,筛选ccRCC血浆差异表达eccDNAs.方法:采用Tn5转座酶标记和二代测序对ccRCC患者(ccRCC组)和健康体检者(健康对照组)的血浆eccDNAs进行测序,分析2组血浆eccDNAs长度分布、基因组注释、环状连接处核苷酸序列模式以及表达的差异.结果:ccRCC组和健康对照组血浆中分别检测出8 568和8 150个eccDNAs.ccRCC组血浆eccDNAs的长度分布、基因注释和核苷酸环状连接模式与健康对照组相比差异无统计学意义.测序结果发现与健康对照组比较,ccRCC组血浆中存在701个差异表达的eccDNAs,其中上调298个,下调403个,并筛选出25个ccRCC组特异性血浆eccDNAs,其中15个序列映射于已知的基因编码区,7个映射于已知的miRNA区,3个映射于已知的lincRNA区.TCGA数据显示11个eccDNAs映射基因的表达与ccRCC患者的生存密切相关.结论:ccRCC患者血浆中存在eccDNAs,且表达谱发生显著改变,血浆eccDNAs有望成为一种新的ccRCC分子标志物.

Abstract

Objective:To investigate the molecular characterization of plasma extrachromosomal circular DNA(eccDNAs)in patients with clear cell renal carcinoma(ccRCC)and to screen for plasma differential expression of eccDNAs in ccRCC patients.Methods:The Tn5-tagmentation and next-generation sequencing(NGS)approach were applied for plasma eccDNAs detection in ccRCC patients and healthy controls.The length distribution,gene annotation,junctional nucleotide motif pattern and expression patterns of plasma eccDNAs were analyzed between ccRCC patients and those of healthy controls.Results:In ccRCC patients and healthy controls 8 568 and 8 150 plasma eccDNAs,respectively.No statistical differences of length distribution,gene annotation and motif signatures were observed between the two groups.Sequencing results showed that there were 701 differentially expressed eccDNAs in the plasma of ccRCC patients,of which 298 were up-regulated and 403 were down-regulated,and 25 ccRCC specific plasma eccDNAs have been screened.Among these eccDNAs,15 sequences mapped to known gene coding regions,7 mapped to known miRNA regions,and 3 mapped to known lincRNA regions.TCGA data showed that the expressions of 11 mapped genes of eccDNAs were significantly associated with the survival of ccRCC patients.Conclusion:This study demonstrated for the first time the presence of eccDNAs in the plasma of ccRCC patients with significantly altered expression profiles,suggesting that plasma eccDNAs is expected to be a new molecular marker for ccRCC.

关键词

染色体外环状DNA/癌,肾细胞/生物标志物/二代测序

Key words

Extrachromosomal circular DNA/Carcinoma,renal cell/Biomarker/Next-generation sequencing

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基金项目

安徽省高校自然科学研究重大项目(KJ2021ZD0102)

出版年

2024
赣南医学院学报
赣南医学院

赣南医学院学报

影响因子:0.622
ISSN:1001-5779
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