Gislefoss Randi Elin, Langseth Hilde, Bolstad Nils, Nustad Kjell, Mørkrid Lars
*Department of Research, Institute of Population-based Cancer Research, Cancer Registry of Norway, Oslo, Norway; and †Department of Medical Biochemistry, Oslo University Hospital, Rikshospitalet-Radiumhospitalet, Oslo, Norway.
Int J Gynecol Cancer. 2015 Nov;25(9):1608-15. doi: 10.1097/IGC.0000000000000532.
Epithelial ovarian cancer is characterized by nonspecific signs and clinical symptoms arising at late stages. Early detection is therefore important and may significantly improve the survival rate. Cancer antigen 125 (CA125) has been the most extensively studied serum biomarker in epithelial ovarian cancer, but low specificity limits its usefulness. A relatively novel biomarker, human epididymis protein 4 (HE4), has shown promise in early detection of the disease. The aim of this study was to investigate how early the tumor marker increases before diagnosis.
METHODS/MATERIALS: A nested case-control design was used to evaluate the performance of HE4 and CA125 in prediagnostic serum samples from the Janus Serumbank. Serial specimens from 120 women with invasive epithelial ovarian cancer were compared with healthy controls. Serum level of CA125, HE4, and cotinine was measured. Spearman correlation and multiple linear regression analyses were used to investigate impact of smoking, age, storage time, and lag time (time from sampling until date of diagnosis).
Spearman correlation showed a strong positive correlation between HE4 and smoking in both cases and controls. Multiple linear regression analyses for pairwise differences between case and control showed that serum level of HE4 and CA125 was significantly increased (P = 0.002 and P < 0.001, respectively) 2 years before diagnosis and that CA125 also was significantly increased up to 4 years before diagnosis (P = 0.002).
The present study showed that a difference between cases and controls in serum concentration of HE4 seemed to be increased 2 years before diagnosis and that CA125 was increased until 4 years before diagnosis.
上皮性卵巢癌的特征是在疾病晚期出现非特异性体征和临床症状。因此，早期检测很重要，可能会显著提高生存率。癌抗原125（CA125）一直是上皮性卵巢癌中研究最广泛的血清生物标志物，但低特异性限制了其用途。一种相对较新的生物标志物，人附睾蛋白4（HE4），在该疾病的早期检测中显示出前景。本研究的目的是调查肿瘤标志物在诊断前多久开始升高。
方法/材料：采用巢式病例对照设计，评估来自雅努斯血清库的诊断前血清样本中HE4和CA125的性能。将120例浸润性上皮性卵巢癌患者的系列标本与健康对照进行比较。测量CA125、HE4和可替宁的血清水平。采用Spearman相关性分析和多元线性回归分析，研究吸烟、年龄、储存时间和滞后时间（从采样到诊断日期的时间）的影响。
Spearman相关性分析显示，病例组和对照组中HE4与吸烟之间均呈强正相关。病例组与对照组之间成对差异的多元线性回归分析表明，HE4和CA125的血清水平在诊断前2年显著升高（分别为P = 0.002和P < 0.001），CA125在诊断前4年也显著升高（P = 0.002）。
本研究表明，病例组与对照组之间HE4血清浓度的差异在诊断前2年似乎增大，而CA125在诊断前4年升高。
