Laval University Cancer Research Center, Hôtel-Dieu-de-Québec, University Hospital Center (CHUQ), 11 Côte du Palais, Québec, Québec, Canada.
Gynecol Oncol. 2012 Dec;127(3):511-5. doi: 10.1016/j.ygyno.2012.09.003. Epub 2012 Sep 9.
A cohort study was conducted to evaluate whether preoperative plasma HE4 levels could predict the occurrence of death (primary endpoint) and progression (secondary endpoint) in women with ovarian cancer (OC).
Between 1998 and 2006, we recruited 136 women newly diagnosed with OC of any FIGO stage at the University Hospital, CHUQ-L'Hôtel-Dieu de Québec, Canada. HE4 was measured using the Abbott's ARCHITECT HE4 assay. Dates of death were obtained by record linkage with the Québec mortality files. Progression was evaluated using the CA-125 or the RECIST criteria, as recommended by the Gynecology Cancer Intergroup. Adjusted hazard ratios (HR) of death and progression, as well as their 95% confidence intervals (CI), were estimated using the Cox proportional hazard regression model.
Preoperative levels of HE4 were strongly associated with all OC standard prognostic factors. HE4 levels increased significantly with age (p=0.02), FIGO stage (p<0.0001), grade (p=0.005), preoperative CA-125 levels (p<0.0001), and residual tumor (p<0.0001). HE4 levels above the median value (394 pmol/L) were significantly associated with mortality (HR=2.17; 95% CI: 1.42-3.32) and progression (HR=1.81; 95% CI: 1.21-2.72). After adjustment for the FIGO stage, which was the only factor significantly associated with prognosis in multivariate analyses, the association of HE4 with death remained statistically significant (HR=1.67; 95% CI: 1.08-2.59). However, the association with progression was no longer significant (HR=1.32; 95% CI: 0.87-1.99).
These results show that preoperative the plasma level of HE4 is a marker of OC aggressiveness and a predictor of death.
本队列研究旨在评估术前血浆 HE4 水平是否可预测卵巢癌（OC）患者的死亡（主要终点）和进展（次要终点）。
1998 年至 2006 年间，我们在加拿大魁北克省舍布鲁克大学医院（CHUQ-L'Hôtel-Dieu de Québec）招募了 136 名新诊断为任何 FIGO 分期的 OC 女性患者。使用 Abbott 的 ARCHITECT HE4 检测试剂盒测量 HE4。通过与魁北克死亡率档案记录链接获得死亡日期。进展采用 CA-125 或 RECIST 标准进行评估，如妇科癌症研究组所推荐的。使用 Cox 比例风险回归模型估计死亡和进展的调整后的风险比（HR）及其 95%置信区间（CI）。
术前 HE4 水平与 OC 的所有标准预后因素均密切相关。HE4 水平随年龄（p=0.02）、FIGO 分期（p<0.0001）、分级（p=0.005）、术前 CA-125 水平（p<0.0001）和残余肿瘤（p<0.0001）显著增加。中位数（394 pmol/L）以上的 HE4 水平与死亡率（HR=2.17；95%CI：1.42-3.32）和进展（HR=1.81；95%CI：1.21-2.72）显著相关。在多变量分析中，仅 FIGO 分期与预后显著相关，将其调整后，HE4 与死亡的相关性仍具有统计学意义（HR=1.67；95%CI：1.08-2.59）。然而，与进展的相关性不再显著（HR=1.32；95%CI：0.87-1.99）。
这些结果表明，术前血浆 HE4 水平是 OC 侵袭性的标志物，也是死亡的预测因子。
