A significant volume of research clearly shows that disease-related methylation changes can be used as biomarkers at all stages of clinical disease management, including risk assessment and predisposition screening through early diagnostics to personalization of patient care and monitoring of the relapse and chronic disease. Thus disease-related methylation changes are an attractive source of the biomarkers that can have significant impact on precision medicine. However, the translation of the research findings in methylation biomarkers field to clinical practice is at the very least not satisfactory. That is mainly because the evidence generated in research studies indicating the utility of the disease-related methylation change to predict clinical outcome is in majority of the cases not sufficient to postulate the diagnostic use of the biomarker. The research studies need to be followed by well-designed and systematic investigations of clinical utility of the biomarker that produce data of sufficient quality to meet regulatory approval for the test to be used to make clinically valid decision. In this review, we describe methylation-based IVD tests currently approved for IVD use or at the advanced stages of the development for the diagnostic use. For each of those tests, we analyze the technologies that the test utilizes for methylation detection as well as describe the types of the clinical studies that were performed to show clinical validity of the test and warrant regulatory approval. The examples reviewed here should help with planning of clinical investigations and delivery of the clinical evidence required for the regulatory approval of potential methylation biomarker based IVD tests.

中文翻译：

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用于体外诊断 IVD 应用的甲基化生物标志物的发展现状。

大量研究清楚地表明，与疾病相关的甲基化变化可用作临床疾病管理各个阶段的生物标志物，包括通过早期诊断进行风险评估和易感性筛查，到患者护理的个性化以及对复发和慢性病的监测。因此，与疾病相关的甲基化变化是一个有吸引力的生物标志物来源，可以对精准医学产生重大影响。然而，将甲基化生物标志物领域的研究成果转化为临床实践至少并不令人满意。这主要是因为研究中产生的证据表明疾病相关甲基化变化可用于预测临床结果在大多数情况下不足以假设生物标志物的诊断用途。在研究研究之后，需要对生物标志物的临床效用进行精心设计和系统的调查，以产生足够质量的数据，以满足监管部门对用于做出临床有效决策的测试的批准。在这篇综述中，我们描述了目前批准用于 IVD 或处于诊断用途开发的高级阶段的基于甲基化的 IVD 测试。对于这些测试中的每一个，我们分析了测试用于甲基化检测的技术，并描述了为证明测试的临床有效性并保证监管批准而进行的临床研究的类型。