Cell-free RNA (cfRNA) allows assessment of health, status, and phenotype of a variety of human organs and is a potential biomarker to non-invasively diagnose numerous diseases. Nevertheless, there is a lack of highly efficient and bias-free cfRNA isolation technologies due to the low abundance and instability of cfRNA. Here, we developed a reproducible and high-efficiency isolation technology for different types of cell-free nucleic acids (containing cfRNA and viral RNA) in serum/plasma based on the inclusion of nucleic acids by metal-organic framework (MOF) materials, which greatly improved the isolation efficiency and was able to preserve RNA integrity compared with the most widely used research kit method. Importantly, the quality of cfRNA extracted by the MOF method is about 10-fold that of the kit method, and the MOF method isolates more than three times as many different RNA types as the kit method. The whole transcriptome mapping characteristics of cfRNA in serum from patients with liver cancer was described and a cfRNA signature with six cfRNAs was identified to diagnose liver cancer with high diagnostic efficiency (area under curve = 0.905 in the independent validation cohort) using this MOF method. Thus, this new MOF isolation technique will advance the field of liquid biopsy, with the potential to diagnose liver cancer.
细胞游离RNA（cfRNA）能够评估多种人体器官的健康、状态及表型，是一种非侵入性诊断多种疾病的潜在生物标志物。然而，由于cfRNA丰度低且不稳定，目前缺乏高效且无偏差的cfRNA分离技术。本研究基于金属有机框架（MOF）材料对核酸的包载作用，开发了一种可重复、高效率的血清/血浆中不同类型细胞游离核酸（含cfRNA及病毒RNA）的分离技术。与最广泛使用的研究试剂盒方法相比，该技术大幅提升了分离效率，并能保持RNA的完整性。重要的是，MOF方法提取的cfRNA质量约为试剂盒方法的10倍，且分离出的不同RNA类型是试剂盒方法的三倍以上。利用此MOF方法，我们描述了肝癌患者血清中cfRNA的全转录组图谱特征，并鉴定出一个包含六种cfRNA的特征组合，用于诊断肝癌具有较高的诊断效率（在独立验证队列中曲线下面积=0.905）。因此，这种新型MOF分离技术将推动液体活检领域的发展，并具备诊断肝癌的潜力。
肿瘤(癌症)患者之家