UOC Patologia Clinica, Ospedale "Luigi Sacco", Via GB Grassi 74, 20157 Milano, Italy.
Department of Biomedical and Clinical Sciences "Luigi Sacco", University of Milan, Milan, Italy.
Clin Chem Lab Med. 2019 Aug 27;57(9):1284-1294. doi: 10.1515/cclm-2018-1111.
Background Measurement of human epididymis protein 4 (HE4) in serum has recently been proposed for clinical use in the framework of ovarian cancer (OvCa). We sought to retrace the translational phase and the clinical implementation steps boosting HE4's clinical value and discuss the effects of its introduction on the diagnostic and management pathways. Methods Meta-analyses of running evidence have preliminarily suggested that HE4 may overcome carbohydrate antigen 125 (CA125) in identifying OvCa, showing however several gaps that need to be considered, i.e. definition of biomarker diagnostic performance in the early detection of OvCa, added diagnostic value, biological and lifestyle factors of variation, and optimal interpretative criteria. Investigation of the influencing factors has shown that renal impairment represents a major limitation for HE4's diagnostic power. On the other hand, the demonstration of the substantial equivalence of results obtained by commercially available assays allows recommending harmonized thresholds for diagnostic purpose, even if the study of HE4's biological variation has clarified that the longitudinal interpretation of the biomarker changes according to the reference change value could be more appropriate. Summary We used HE4 as an example for describing the long and bumpy road for making a new biomarker a reality, and the issues that should be checked and the information that should be provided in moving a novel biomarker from its discovery to an effective clinical adoption.
背景 人附睾蛋白 4（HE4）在血清中的测量最近被提议用于卵巢癌（OvCa）的临床应用框架。我们试图追溯提升 HE4 临床价值的转化阶段和临床实施步骤，并讨论其引入对诊断和管理途径的影响。 方法 对现有证据的荟萃分析初步表明，HE4 可能在识别 OvCa 方面优于糖类抗原 125（CA125），但仍存在一些需要考虑的差距，即生物标志物诊断性能在 OvCa 早期检测中的定义、附加诊断价值、生物和生活方式因素的变化以及最佳解释标准。对影响因素的研究表明，肾功能不全是 HE4 诊断能力的主要限制。另一方面，商业上可用的检测方法所获得的结果具有实质性等效性的证明，允许为诊断目的推荐协调的阈值，即使对 HE4 生物学变异性的研究表明，根据参考变化值对生物标志物变化的纵向解释可能更合适。 总结 我们以 HE4 为例，描述了将新的生物标志物变为现实的漫长而坎坷的道路，以及在将新的生物标志物从发现到有效临床应用的过程中需要检查的问题和需要提供的信息。
