Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Wilmot Cancer Institute, University of Rochester, Rochester, NY, USA.
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Medical University of South Carolina, Charleston, SC, USA.
Tumour Biol. 2022;44(1):205-213. doi: 10.3233/TUB-220016.
CA125 is the gold standard serum biomarker for monitoring patients with epithelial ovarian cancer (EOC). Human epididymal protein 4 (HE4) is a novel serum biomarker for EOC patients.
The objective of this trial was to examine the utility of measuring serum HE4 levels for monitoring EOC patients and to compare HE4 performance parameters to serum CA125.
A retrospective trial using residual longitudinal serum samples drawn during treatment and monitoring from EOC patients. Serum CA125 and HE4 levels were analyzed at each time point, and a velocity of change was calculated and correlated with clinical status. The null hypothesis was that HE4 is inferior to CA125, and this was tested using concordance and two-sided Fisher's exact testing. McNemar's test was used to assess the overall agreement of the two assays with the clinical status.
A total of 129 patients with 272 separate clinical periods and 1739 events (serum samples) were evaluated. Using a 25% change in serum biomarker levels to indicate change in disease status, the accuracy and NPV determined for HE4 versus CA125 were 81.8% versus 82.6% (p = 0.846) and 87.4% versus 89.7% (p = 0.082), respectively. Concordance comparison of HE4 accuracy / CA125 accuracy was 0.990, indicating HE4 was not inferior to CA125 (McNemar's test p-value = 0.522). Performing a velocity of change analysis, the accuracy and NPV determined for HE4 versus CA125 were 78.3% versus 78.6% (p = 0.995) and 74.9% versus 76.3% (p = 0.815), respectively. Concordance comparison of HE4 velocity accuracy / CA125 velocity accuracy was 0.996, again indicating HE4 was not inferior to CA125 (McNemar's test p-value = 0.884). The combination of HE4 and CA125 velocity changes showed a similar accuracy of 81.3% (p = 0.797 compared to HE4 and CA125 alone) and NPV of 81.1% (p≥0.172 compared to HE4 and CA125 alone), and an increased sensitivity of 70.5% (p≤0.070 compared to HE4 and CA125 alone).
HE4 is equivalent to CA125 for monitoring of EOC patients. The combination of CA125 and HE4 velocities is superior to either marker alone.
CA125 是监测上皮性卵巢癌（EOC）患者的金标准血清生物标志物。人附睾蛋白 4（HE4）是一种新型的 EOC 患者血清生物标志物。
本试验旨在研究测量血清 HE4 水平监测 EOC 患者的效用，并比较 HE4 性能参数与血清 CA125。
使用在 EOC 患者治疗和监测期间残留的纵向血清样本进行回顾性试验。在每个时间点分析血清 CA125 和 HE4 水平，并计算变化速度并与临床状况相关联。零假设是 HE4 劣于 CA125，使用一致性和双侧 Fisher 精确检验对其进行检验。McNemar 检验用于评估两种检测方法与临床状态的总体一致性。
共评估了 129 名患者的 272 个单独的临床期和 1739 个事件（血清样本）。使用血清生物标志物水平变化 25%来指示疾病状态的变化，HE4 与 CA125 的准确性和阴性预测值分别为 81.8%与 82.6%（p=0.846）和 87.4%与 89.7%（p=0.082）。HE4 准确性/CA125 准确性的一致性比较为 0.990，表明 HE4 并不劣于 CA125（McNemar 检验 p 值=0.522）。进行速度变化分析，HE4 与 CA125 的准确性和阴性预测值分别为 78.3%与 78.6%（p=0.995）和 74.9%与 76.3%（p=0.815）。HE4 速度准确性/CA125 速度准确性的一致性比较为 0.996，再次表明 HE4 并不劣于 CA125（McNemar 检验 p 值=0.884）。HE4 和 CA125 速度变化的组合显示出相似的准确性为 81.3%（与单独使用 HE4 和 CA125 相比，p=0.797）和阴性预测值为 81.1%（与单独使用 HE4 和 CA125 相比，p≥0.172），敏感性增加了 70.5%（与单独使用 HE4 和 CA125 相比，p≤0.070）。
HE4 与 CA125 监测 EOC 患者的效果相当。CA125 和 HE4 速度的组合优于任何单一标志物。
