Department of Oncology, Vejle Hospital, Kabbeltoft 25, Vejle, Denmark.
Int J Gynecol Cancer. 2012 Nov;22(9):1474-82. doi: 10.1097/IGC.0b013e3182681cfd.
A risk-of-ovarian-malignancy algorithm (ROMA) based on human epididymis protein 4 (HE4) and CA-125 has been reported to categorize women with a pelvic mass into high or low risk of ovarian malignancy. Originally, the ROMA score was developed for diagnostic purposes and the clinical application of HE4 for other purposes such as a predictor of survival or platinum resistance has not been extensively investigated. The objective of the present study was to evaluate the prognostic importance of prechemotherapy combined levels of HE4 and CA-125 and prediction of platinum resistance. Furthermore, we wanted to investigate the dynamics of the markers during treatment.
Serum from 137 patients with newly diagnosed serous ovarian cancer was analyzed for CA-125 and HE4 using ELISAs in a training data set. Patients with high levels (upper third percentiles) of both HE4 and CA-125 were classified as high-risk patients. Data were validated in an independent data set of an additional 94 patients. HE4 and CA-125 were also analyzed at all cycles of subsequent chemotherapy.
The combined score of HE4 and CA-125 was highly predictive of both progression-free and overall survival in univariate as well as multivariate survival analysis. Values in the upper third percentiles (66th) were significantly associated with decreased progression-free and overall survival in both the training and in the validation set (P < 0.05 in all analyses).The positive predictive value in relation to platinum resistance was higher for the combination of markers than for the markers individually. The positive predictive values were 64.3% and 60.7% for combined CA-125/HE4 in the training and validation sets, respectively.
The combination of HE4 and CA-125 levels at baseline just before initiation of chemotherapy was significantly associated with decreased progression-free and overall survival and to some extent with platinum resistance.
基于人附睾蛋白 4（HE4）和 CA-125 的卵巢恶性肿瘤风险算法（ROMA）已被报道可将盆腔肿块患者分为卵巢恶性肿瘤高风险或低风险。最初，ROMA 评分是为诊断目的而开发的，HE4 用于其他目的（如预测生存或铂耐药）的临床应用尚未广泛研究。本研究的目的是评估化疗前联合 HE4 和 CA-125 水平的预后重要性和预测铂耐药。此外，我们还希望研究标志物在治疗过程中的动态变化。
使用 ELISA 在训练数据集中分析了 137 例新诊断的浆液性卵巢癌患者的血清 CA-125 和 HE4。将 HE4 和 CA-125 水平均处于较高水平（上三分之一百分位）的患者归类为高危患者。在另外 94 例患者的独立数据集中验证了数据。还在随后化疗的所有周期中分析了 HE4 和 CA-125。
HE4 和 CA-125 的联合评分在单变量和多变量生存分析中均高度预测无进展生存期和总生存期。在上三分之一百分位（第 66 位）的患者值在训练集和验证集中均与无进展生存期和总生存期降低显著相关（所有分析中 P<0.05）。与铂耐药相关的阳性预测值，标志物联合检测的阳性预测值高于单独检测。在训练集和验证集中，联合 CA-125/HE4 的阳性预测值分别为 64.3%和 60.7%。
化疗前基线时 HE4 和 CA-125 水平的联合与无进展生存期和总生存期降低显著相关，在一定程度上与铂耐药相关。
