A comprehensive evaluation of full-spectrum cell-free RNAs highlights cell-free RNA fragments for early-stage hepatocellular carcinoma detection.

A comprehensive evaluation of full-spectrum cell-free RNAs highlights cell-free RNA fragments for early-stage hepatocellular carcinoma detection.
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DOI:
10.1016/j.ebiom.2023.104645
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发表时间:
2023-07
期刊:
影响因子:
11.1
通讯作者:
Yin, Jianhua
Yin, Jianhua
中科院分区:
医学1区
文献类型:
--
作者:
Ning, Chun;Cai, Peng;Liu, Xiaofan;Li, Guangtao;Bao, Pengfei;Yan, Lu;Ning, Meng;Tang, Kaichen;Luo, Yi;Guo, Hua;Wang, Yunjiu;Wang, Zhuoran;Chen, Lu;Lu, Zhi John;Yin, Jianhua

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各种研究已经报道了无细胞rna (cfRNAs)作为检测肝细胞癌(HCC)的无创生物标志物。然而,它们还没有得到独立的验证,有些结果是矛盾的。我们对各种类型的cfRNA生物标志物进行了综合评估,并充分挖掘了cfRNA新特征的生物标志物潜力。我们首先系统地回顾了已报道的cfRNA生物标志物,并计算了失调的转录后事件和cfRNA片段。在3个独立的多中心队列中,我们使用RT-qPCR进一步选择了6个cfRNAs,使用机器学习构建了一个名为HCCMDP的AFP面板,并在内部和外部验证了HCCMDP的性能。通过对5个cfRNA-seq数据集的系统回顾和分析,我们确定了23个候选cfRNA生物标志物。值得注意的是,我们定义了cfRNA结构域来系统地描述cfRNA片段。在验证队列(n = 183)中,cfRNA片段更有可能被验证,而circRNA和嵌合RNA候选物作为基于qpcr的生物标志物既不丰富也不稳定。在算法开发队列(= 287)中,我们构建并测试了包含6个cfRNA标记和AFP的面板HCCMDP。在独立验证队列(= 171)中,HCCMDP能够区分HCC患者与对照组(all: AUC = 0.925; CHB: AUC = 0.909; LC: AUC = 0.916),在区分早期HCC患者方面表现良好(all: AUC = 0.936; CHB: AUC = 0.917; LC: AUC = 0.928)。本研究综合评价了全谱cfRNA用于HCC检测的生物标志物类型,强调了cfRNA片段作为HCC检测中有前景的生物标志物类型,并提供了面板HCCMDP。(973计划)。
Various studies have reported cell-free RNAs (cfRNAs) as noninvasive biomarkers for detecting hepatocellular carcinoma (HCC). However, they have not been independently validated, and some results are contradictory. We provided a comprehensive evaluation of various types of cfRNA biomarkers and a full mining of the biomarker potential of new features of cfRNA. We first systematically reviewed reported cfRNA biomarkers and calculated dysregulated post-transcriptional events and cfRNA fragments. In 3 independent multicentre cohorts, we further selected 6 cfRNAs using RT-qPCR, built a panel called HCCMDP with AFP using machine learning, and internally and externally validated HCCMDP's performance. We identified 23 cfRNA biomarker candidates from a systematic review and analysis of 5 cfRNA-seq datasets. Notably, we defined the cfRNA domain to describe cfRNA fragments systematically. In the verification cohort (n = 183), cfRNA fragments were more likely to be verified, while circRNA and chimeric RNA candidates were neither abundant nor stable as qPCR-based biomarkers. In the algorithm development cohort ( = 287), we build and test the panel HCCMDP with 6 cfRNA markers and AFP. In the independent validation cohort ( = 171), HCCMDP can distinguish HCC patients from control groups (all: AUC = 0.925; CHB: AUC = 0.909; LC: AUC = 0.916), and performs well in distinguishing early-stage HCC patients (all: AUC = 0.936; CHB: AUC = 0.917; LC: AUC = 0.928). This study comprehensively evaluated full-spectrum cfRNA biomarker types for HCC detection, highlighted the cfRNA fragment as a promising biomarker type in HCC detection, and provided a panel HCCMDP. , and The (973 program).
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发表时间: 2010-03-15
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