Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea.
Int J Cancer. 2012 Mar 1;130(5):1136-44. doi: 10.1002/ijc.26129. Epub 2011 Jun 14.
Human epididymis protein 4 (HE4) is a new biomarker for the detection of ovarian cancer. We evaluated the analytical performance of a novel automated HE4 assay and established reference ranges of HE4 and CA125. We also compared the diagnostic performance of both biomarkers for ovarian cancer. Precision performances and linearity of the HE4 assay were assessed. Serum samples from 2,182 healthy and 72 pregnant women were also assayed for HE4 and CA125, and the 95%, 97.5% and 99% reference limits for both markers were calculated. Additionally, sera from 66 ovarian cancer and 257 benign gynecologic disease patients were tested to validate reference ranges and diagnostic performances. The total precision of the HE4 assay was <5% coefficient of variation for most of the levels evaluated. The linearity range of this assay was from 15.0 to 1100.0 pmol/L. The 97.5% upper reference limits for HE4 and CA125 were 33.2 pmol/L (95% confidence interval [CI], 32.2-34.0) and 38.3 U/mL (95% CI, 35.1-41.5), respectively. Using these values as cutoff points, the sensitivity and specificity of HE4 for differentiating ovarian cancer from benign gynecologic diseases and healthy individuals were 90.9% and 94.1%, and those of CA125 were 72.7% and 94.4%. The receiver operating characteristic-area under the curve values of HE4 and CA125 for discriminating ovarian cancer from age-matched control were 0.94 and 0.86, respectively, and they were statistically different (p = 0.0095). The new automated HE4 assay showed good analytical and diagnostic performances. The reference limits established in our study could be used as cutoff levels to facilitate more accurate diagnosis of ovarian cancer in Asian population.
人附睾蛋白 4（HE4）是一种新的卵巢癌检测生物标志物。我们评估了一种新型自动化 HE4 检测方法的分析性能，并建立了 HE4 和 CA125 的参考范围。我们还比较了这两种生物标志物对卵巢癌的诊断性能。评估了 HE4 检测的精密度性能和线性度。还检测了 2182 例健康女性和 72 例妊娠女性的血清样本，用于 HE4 和 CA125，并计算了这两种标志物的 95%、97.5%和 99%参考限值。此外，还检测了 66 例卵巢癌和 257 例良性妇科疾病患者的血清，以验证参考范围和诊断性能。该 HE4 检测的总精密度在评估的大多数水平下<5%的变异系数。该检测的线性范围为 15.0 至 1100.0 pmol/L。HE4 和 CA125 的 97.5%上限参考值分别为 33.2 pmol/L（95%置信区间 [CI]，32.2-34.0）和 38.3 U/mL（95%CI，35.1-41.5）。使用这些值作为截止值，HE4 区分卵巢癌与良性妇科疾病和健康个体的敏感性和特异性分别为 90.9%和 94.1%，CA125 的敏感性和特异性分别为 72.7%和 94.4%。HE4 和 CA125 用于区分卵巢癌与年龄匹配对照的受试者工作特征曲线下面积值分别为 0.94 和 0.86，差异有统计学意义（p=0.0095）。新型自动化 HE4 检测方法具有良好的分析和诊断性能。我们研究中建立的参考范围可作为截止值，有助于更准确地诊断亚洲人群中的卵巢癌。
