The significance of urine extracellular vesicle DNA methylation detection in the diagnosis and classification of prostate cancer

IF 13 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Ting Ding, Yanjun Diao, Ruiqing Fu, Chengxiang Gong, Qiye He, Weixiang He, Longlong Zhang, Xiaojian Yang, Xianfei Zeng, Lijuan Yu, Jiayun Liu, Weimei Shi, Kang Zhang, Xiaoke Hao
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引用次数: 0

Abstract

Introduction

As one of the most common malignant tumors in men, prostate cancer (PCa) still lacks convenient, non-invasive and highly specific diagnostic markers. The advantages of Extracellular vesicle (EV) DNA in tumor diagnosis have gradually attracted the attention of researchers. However, methylation detection, which is more advantageous than mutation detection in tumor diagnosis, has not been widely practiced in EV DNA, and its value in PCa diagnosis also remains underexplored.

Objectives

This study aims to establish and optimize an EV DNA methylation detection system and evaluate its diagnostic and classification potential for PCa.

Methods

We characterized EV DNA biological properties, optimized pretreatment strategies, validated its correlation with genomic DNA methylation, and explored urine EV DNA methylation targets in 86 benign prostatic hyperplasia (BPH) and 109 PCa patients across three cohorts (screening: 30 BPH/33 PCa; training: 27 BPH/30 PCa; validation: 29 BPH/46 PCa).

Results

Heterogeneous biological characteristics were observed among DNA from different subtypes of EV, but methylation profiles remained consistent across subtypes and post-DNase I treatment. EV DNA accurately reflected the methylation state of source cell genomic DNA. By combining our screening results with data from the TCGA database and previously reported, we developed a panel consisting of 667 PCa-specific methylation targets for detection. Among these, six methylation sites (MACF1、LINC01359-1、LINC01359-2、ADCY4、GAPLINC、C19orf25) demonstrated high diagnostic value for PCa, enabling construction of PCa and aggressive PCa differential diagnosis model with AUCs up to 0.74 and 0.91 respectively. The diagnostic value of these six markers was further confirmed using methylight PCR in the validation cohort which also displayed promising performance as a tool for diagnosing PCa.

Conclusion

This study highlights the potential of urine EV DNA methylation as a novel diagnostic marker for PCa and lays a foundation for future EV DNA research.

Abstract Image

尿细胞外囊泡DNA甲基化检测在前列腺癌诊断和分型中的意义
前列腺癌(prostate cancer, PCa)是男性最常见的恶性肿瘤之一,目前仍缺乏方便、无创、高特异性的诊断标志物。细胞外囊泡(EV) DNA在肿瘤诊断中的优势逐渐引起研究人员的重视。然而,甲基化检测在肿瘤诊断中比突变检测更有利,但在EV DNA中尚未广泛应用,其在PCa诊断中的价值也有待进一步探索。目的建立并优化EV DNA甲基化检测系统,评价其对前列腺癌的诊断和分类潜力。方法研究了EV DNA的生物学特性,优化了预处理策略,验证了其与基因组DNA甲基化的相关性,并对86例良性前列腺增生(BPH)和109例前列腺增生患者(筛选:30例BPH/33例PCa;训练:27例BPH/30例PCa;验证:29例BPH/46例PCa)的尿液EV DNA甲基化靶点进行了探讨。结果来自不同亚型EV的DNA具有不同的生物学特征,但不同亚型和DNA酶I处理后的甲基化谱保持一致。EV DNA准确反映了源细胞基因组DNA的甲基化状态。通过将我们的筛选结果与TCGA数据库和先前报道的数据相结合,我们开发了一个由667个pca特异性甲基化靶点组成的检测小组。其中,6个甲基化位点(MACF1、LINC01359-1、LINC01359-2、ADCY4、GAPLINC、C19orf25)对PCa具有较高的诊断价值,可构建PCa和侵袭性PCa鉴别诊断模型,auc分别高达0.74和0.91。在验证队列中使用甲基光PCR进一步证实了这六个标记的诊断价值,作为诊断PCa的工具也显示出有希望的性能。结论尿液EV DNA甲基化可作为一种新的前列腺癌诊断标志物,为未来EV DNA的研究奠定基础。
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来源期刊
Journal of Advanced Research
Journal of Advanced Research Multidisciplinary-Multidisciplinary
CiteScore
21.60
自引率
0.90%
发文量
280
审稿时长
12 weeks
期刊介绍: Journal of Advanced Research (J. Adv. Res.) is an applied/natural sciences, peer-reviewed journal that focuses on interdisciplinary research. The journal aims to contribute to applied research and knowledge worldwide through the publication of original and high-quality research articles in the fields of Medicine, Pharmaceutical Sciences, Dentistry, Physical Therapy, Veterinary Medicine, and Basic and Biological Sciences. The following abstracting and indexing services cover the Journal of Advanced Research: PubMed/Medline, Essential Science Indicators, Web of Science, Scopus, PubMed Central, PubMed, Science Citation Index Expanded, Directory of Open Access Journals (DOAJ), and INSPEC.
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