全面确定cfDNA分子的末端
Peiyong Jiang1, Mary-Jane L Ma2, Rong Qiao2
1Centre for Novostics, Hong Kong Science Park, Pak Shek Kok, New Territories, Hong Kong SAR, China; Li Ka Shing Institute of Health Sciences, the Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China; Department of Chemical Pathology, the Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China; State Key Laboratory of Translational Oncology, the Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China.
来自无细胞DNA (cfDNA) 3'端的新片段标记物改善了肝细胞癌 (HCC) 的检测. 这种新的方法增强了用于癌症诊断的液体活检.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 生物标志物 生物标志物
背景情况:
- 无细胞DNA (cfDNA) 末端动机是癌症检测中的新兴碎片组生物标志物.
- 之前的研究忽视了3'cfDNA末端,因为测序文物,限制了生物标志物的发现.
研究的目的:
- 研究cfDNA中的原生5'和3'末端基因 (EM5,EM3) 和相关的核酸基因 (PREM,POEM).
- 评估这些新的肝细胞癌 (HCC) 断片学标记物的诊断性能.
- 探索基于碎片学的甲基化分析 (3' FRAGMA) 和用于增强癌症检测的先进测序技术.
主要方法:
- 使用单链库准备"2-end测序"来分析本地cfDNA末端.
- 开发和应用前期动机 (PREM) 和后期动机 (POEM) 分析.
- 实施了基于碎片学的甲基化分析 (3' FRAGMA) 和"4端测序".
主要成果:
- 碎片学标记器在HCC检测中实现了0.95的AUC.
- 3' FRAGMA显著改善了HCC检测,其AUC为0.97.
- "四端测序"进一步增强了基于fragmentomics的癌症检测能力.
结论:
- 原生cfDNA末端模式,包括3'末端和相关的核酸模式,是HCC检测的强大生物标志物.
- 对cfDNA末端的高级测序和甲基化分析代表了液体活检的重大进步.
- 整体终端分析为cfDNA碎片化生物学提供了新的见解,并改善了癌症诊断.
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