Genet Sylvia A A M, Visser Esther, van den Borne Ben E E M, Soud Maggy Youssef-El, Belderbos Huub N A, Stege Gerben, de Saegher Marleen E A, Eduati Federica, Broeren Maarten A C, van Dongen Joost, Brunsveld Luc, van de Kerkhof Daan, Scharnhorst Volkher
Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands.
Expert Center Clinical Chemistry Eindhoven, Eindhoven, The Netherlands.
Oncotarget. 2020 Jul 7;11(27):2660-2668. doi: 10.18632/oncotarget.27664.
Neuron-specific enolase (NSE) is a well-known biomarker for the diagnosis, prognosis and treatment monitoring of small-cell lung cancer (SCLC). Nevertheless, its clinical applicability is limited since serum NSE levels are influenced by hemolysis, leading to falsely elevated results. Therefore, this study aimed to develop a hemolysis correction equation and evaluate its role in SCLC diagnostics. Two serum pools were spiked with increasing amounts of hemolysate obtained from multiple individuals. A hemolysis correction equation was obtained by analyzing the relationship between the measured NSE concentration and the degree of hemolysis. The equation was validated using intentionally hemolyzed serum samples, which showed that the correction was accurate for samples with an H-index up to 30 μmol/L. Correction of the measured NSE concentration in patients suspected of lung cancer caused an increase in AUC and a significantly lower cut-off value for SCLC detection when compared to uncorrected results. Therefore, a hemolysis correction equation should be used to correct falsely elevated NSE concentrations. Results of samples with an H-index above 30 μmol/L should not be reported to clinicians. Application of the equation illustrates the importance of hemolysis correction in SCLC diagnostics and questions the correctness of the currently used diagnostic cut-off value.
神经元特异性烯醇化酶（NSE）是小细胞肺癌（SCLC）诊断、预后及治疗监测中一种广为人知的生物标志物。然而，其临床适用性有限，因为血清NSE水平受溶血影响，会导致结果假性升高。因此，本研究旨在建立一个溶血校正方程，并评估其在SCLC诊断中的作用。向两个血清混合样本中加入来自多个个体的不同量溶血产物。通过分析测得的NSE浓度与溶血程度之间的关系获得溶血校正方程。使用故意溶血的血清样本对该方程进行验证，结果表明，对于H指数高达30 μmol/L的样本，校正准确。与未校正结果相比，对疑似肺癌患者测得的NSE浓度进行校正后，SCLC检测的曲线下面积（AUC）增加，截断值显著降低。因此，应使用溶血校正方程来校正假性升高的NSE浓度。H指数高于30 μmol/L的样本结果不应报告给临床医生。该方程的应用说明了溶血校正在SCLC诊断中的重要性，并对目前使用的诊断截断值的正确性提出了质疑。
