PDF(Pubmed)
Abstract：
Glioma represents the most common central nervous system neoplasm in adults. Current classification scheme utilizes molecular alterations, particularly IDH1.R132H, to stratify lesions into distinct prognostic groups. Identification of the single nucleotide variant through traditional tissue biopsy assessment poses procedural risks and does not fully reflect the heterogeneous and evolving tumor landscape. Here, we introduce a liquid biopsy assay, mt-IDH1dx. The blood-based test allows minimally invasive detection of tumor-derived extracellular vesicle RNA using only 2 ml plasma volume. We perform rigorous, blinded validation testing across the study population (n = 133), comprising of IDH1.R132H patients (n = 80), IDH1 wild-type gliomas (n = 44), and age matched healthy controls (n = 9). Results from our plasma testing demonstrate an overall sensitivity of 75.0% (95% CI: 64.1%-84.0%), specificity 88.7% (95% CI: 77.0%-95.7%), positive predictive value 90.9%, and negative predictive value 70.1% compared to the tissue gold standard. In addition to fundamental diagnostic applications, the study also highlights the utility of mt-IDH1dx platform for blood-based monitoring and surveillance, offering valuable prognostic information. Finally, the optimized workflow enables rapid and efficient completion of both tumor tissue and plasma testing in under 4 hours from the time of sampling.
摘要：
胶质瘤是成人最常见的中枢神经系统肿瘤。目前的分类方案利用分子改变，尤其是IDH1。R132H,将病变分层为不同的预后组。通过传统的组织活检评估来鉴定单核苷酸变体会带来程序风险，并且不能充分反映异质性和不断发展的肿瘤景观。这里,我们介绍一种液体活检方法，mt-IDH1dx.基于血液的测试允许仅使用2ml血浆体积对肿瘤来源的细胞外囊泡RNA进行微创检测。我们执行严格，在研究人群中进行盲化验证测试(n=133)，由IDH1组成。R132H患者（n=80），IDH1野生型胶质瘤（n=44），和年龄匹配的健康对照（n=9）。我们的血浆测试结果显示总体灵敏度为75.0%(95%CI:64.1%-84.0%),特异性88.7%（95%CI：77.0%-95.7%），阳性预测值90.9%，与组织金标准相比，阴性预测值为70.1%。除了基本的诊断应用，该研究还强调了mt-IDH1dx平台用于基于血液的监测和监视的实用性，提供有价值的预后信息。最后,优化的工作流程可在取样后4小时内快速有效地完成肿瘤组织和血浆检测.
