Yang Qian, Hai Ling, Niu Yan, Wen Jian-Xun, Yang Dan-Ni, Cha Su-Na, Zhu Hong-Zhe, Yan Cheng, Yan Li, Wang Ying-Jun, Zheng Wen-Qi, Hu Zhi-De, Zhang Lei
Department of Laboratory Medicine, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
Key Laboratory for Biomarkers, Inner Mongolia Medical University, Hohhot, China.
J Thorac Dis. 2025 Aug 31;17(8):5951-5959. doi: 10.21037/jtd-2025-342. Epub 2025 Aug 28.
Soluble biomarkers in pleural fluid are a promising diagnostic tool for malignant pleural effusion (MPE) due to their advantages of low cost, short turnaround time, and less invasiveness. Several studies have investigated the value of pleural fluid human epididymis secretory protein 4 (HE4) in detecting MPE, but the results varied. This systematic review and meta-analysis aimed to assess the value of pleural fluid HE4 in differentiating between MPE and benign pleural effusion (BPE).
The PubMed and Web of Science databases were used to identify eligible studies regarding the diagnostic value of pleural fluid HE4 for MPE and published before May 1, 2025. We extracted the following information from all eligible studies: first author, country, sample sizes of MPE and BPE, publication year, study design (e.g., prospective, retrospective), HE4 assay, the definition for MPE, the area under the curve (AUC) of HE4, sensitivity, specificity, and corresponding threshold. We used the revised Quality Assessment for Diagnostic Accuracy Studies tool (QUADAS-2) to assess the risk of bias in eligible studies. The bivariate model was used to calculate the pooled sensitivity and specificity. The summary receiver operating characteristic (sROC) curve was constructed to estimate the value of HE4 for differentiating between MPE and BPE. Deeks's test was employed to assess the risk of publication bias.
Seven studies with 1,216 patients (592 MPEs and 624 BPEs) were included in this meta-analysis. The meta-analysis revealed HE4 had a pooled sensitivity of 0.59 [95% confidence interval (CI): 0.43-0.74] and specificity of 0.94 (95% CI: 0.82-0.98). HE4 had an AUC of 0.83 (95% CI: 0.80-0.86). No significant publication bias across the included studies was observed. The primary risk of bias was the representativeness of the cohort, data-driven threshold selection, and particle verification bias.
Pleural fluid HE4 has a moderate value for differentiating between MPE and BPE. However, it cannot be used to confirm or rule out MPE when used alone.
由于具有成本低、周转时间短和侵入性小等优点，胸腔积液中的可溶性生物标志物是诊断恶性胸腔积液（MPE）的一种有前景的工具。多项研究探讨了胸腔积液中人附睾分泌蛋白4（HE4）在检测MPE中的价值，但结果各异。本系统评价和荟萃分析旨在评估胸腔积液HE4在鉴别MPE与良性胸腔积液（BPE）中的价值。
利用PubMed和Web of Science数据库检索2025年5月1日前发表的关于胸腔积液HE4对MPE诊断价值的符合条件的研究。我们从所有符合条件的研究中提取以下信息：第一作者、国家、MPE和BPE的样本量、发表年份、研究设计（如前瞻性、回顾性）、HE4检测方法、MPE的定义、HE4的曲线下面积（AUC）、敏感性、特异性及相应阈值。我们使用诊断准确性研究质量评估修订工具（QUADAS-2）评估符合条件研究中的偏倚风险。采用双变量模型计算合并敏感性和特异性。构建汇总受试者工作特征（sROC）曲线以评估HE4在鉴别MPE与BPE中的价值。采用Deeks检验评估发表偏倚风险。
本荟萃分析纳入了7项研究，共1216例患者（592例MPE和624例BPE）。荟萃分析显示，HE4的合并敏感性为0.59[95%置信区间（CI）：0.43-0.74]，特异性为0.94（95%CI：0.82-0.98）。HE4的AUC为0.83（95%CI：0.80-0.86）。纳入研究中未观察到明显的发表偏倚。主要偏倚风险在于队列的代表性、数据驱动的阈值选择和颗粒验证偏倚。
胸腔积液HE4在鉴别MPE与BPE方面具有中等价值。然而，单独使用时不能用于确诊或排除MPE。
