Bérgamo Silvia, Trapé Jaume, González-García Laura, González-Fernández Carolina, Vergara Carme, la-Torre Noelia de-, Bosch-Presegué Laia, Otero-Viñas Marta, Catot Silvia, Crespo-Casal Manuel, Rives-Jimenez Jose, Arnau Anna, Costa Roser, Cugat José Ramón, Gonzalez-Sánchez Francesc, Pla-Salas Xavier, Sant Francesc
Department of Laboratory Medicine Althaia Xarxa Assistencial Universitària Manresa, Spain; Tissue Repair and Regeneration Laboratory (TR2Lab), Institut de Recerca i Innovació en Ciències de la Vida i de la Salut a la Catalunya Central (IrisCC), Ctra. de Roda, 70 08500 Vic, Barcelona, Spain; Doctoral School, University of Vic - Central University of Catalonia, 08500 Vic, Barcelona, Spain.
Department of Laboratory Medicine Althaia Xarxa Assistencial Universitària Manresa, Spain; Tissue Repair and Regeneration Laboratory (TR2Lab), Institut de Recerca i Innovació en Ciències de la Vida i de la Salut a la Catalunya Central (IrisCC), Ctra. de Roda, 70 08500 Vic, Barcelona, Spain; Faculty of Medicine, University of Vic - Central University of Catalonia, 08500 Vic, Barcelona, Spain.
Clin Chim Acta. 2025 Jan 30;566:120027. doi: 10.1016/j.cca.2024.120027. Epub 2024 Nov 9.
Pleural effusions are challenging to diagnose, with approximately 20-50% of malignant effusions not diagnosed by cytology. Human epididymal protein 4 (HE4) may be useful in the differential diagnosis of pleural effusions. In serum, this biomarker shows false-positive results in some benign diseases. The aim of this study was to evaluate the diagnostic utility of HE4 in this setting and to identify false positives.
Concentrations of HE4, adenosine deaminase, % polynuclear cells, and C-reactive protein, were determined in 238 pleural fluid samples and the estimated glomerular filtration rate (eGFr) in serum.
HE4 values differed significantly (p < 0.01) between malignant [median (IQR)] [1065 (2085)] pmol/L and benign effusions [699 (589)] pmol/L. HE4 concentrations in gynecological and pulmonary tumors were significantly higher than in other tumors. For a cut-off point of 3050 pmol/L, 22 % sensitivity and 100 % specificity were obtained. In patients with benign disease, significant increases in HE4 were identified only in those with eGFr < 30 mL/min/1.73 m [1050(596)] pmol/L, and not in those with eGFr > 30 mL/min/1.73 m [597(532)] pmol/L). Two cut-offs were established for maximum specificity, depending on the eGFr: 3050 pmol/L for eGFr < 30 mL/min/1.73 m and 1992 pmol/L for eGFr > 30 mL/min/1.73 m. A sensitivity of 28.5 % was obtained for patients with eGFr > 30 mL/min/1.73 m and 36.3 % for patients with eGFr < 30 mL/min/1.73 m. The sensitivity using a specific cut-off point was 29.7 %.
The determination of HE4 in pleural fluids demonstrates high specificity and low sensitivity. The use of specific cutoff points that are clinically adjusted improves sensitivity while maintaining maximum specificity.
胸腔积液的诊断具有挑战性，约20%-50%的恶性胸腔积液无法通过细胞学检查确诊。人附睾蛋白4（HE4）可能有助于胸腔积液的鉴别诊断。在血清中，这种生物标志物在一些良性疾病中会出现假阳性结果。本研究的目的是评估HE4在此情况下的诊断效用，并识别假阳性结果。
测定了238份胸腔积液样本中HE4、腺苷脱氨酶、多形核细胞百分比和C反应蛋白的浓度，以及血清中的估计肾小球滤过率（eGFr）。
恶性胸腔积液[中位数（四分位间距）][1065（2085）]pmol/L与良性胸腔积液[699（589）]pmol/L之间的HE4值差异显著（p<0.01）。妇科和肺部肿瘤中的HE4浓度显著高于其他肿瘤。对于3050 pmol/L的截断点，敏感性为22%，特异性为100%。在良性疾病患者中，仅在估计肾小球滤过率<30 mL/min/1.73 m [1050(596)] pmol/L的患者中发现HE4显著升高，而在估计肾小球滤过率>30 mL/min/1.73 m [597(532)] pmol/L的患者中未发现。根据估计肾小球滤过率确定了两个最大特异性的截断点：估计肾小球滤过率<30 mL/min/1.73 m时为3050 pmol/L，估计肾小球滤过率>30 mL/min/1.73 m时为1992 pmol/L。估计肾小球滤过率>30 mL/min/1.73 m的患者敏感性为28.5%，估计肾小球滤过率<30 mL/min/1.73 m的患者敏感性为36.3%。使用特定截断点时的敏感性为29.7%。
测定胸腔积液中的HE4显示出高特异性和低敏感性。使用临床调整后的特定截断点可提高敏感性，同时保持最大特异性。
