Cheng Hong-Yan, Zeng Lin, Ye Xue, Ma Rui-Qiong, Tang Zhi-Jian, Chu Hong-Ling, Zhao Yi-Ming, Zhu Li-Rong, Gao Yu-Nong, Chang Xiao-Hong, Cui Heng
Department of Obstetrics and Gynecology, Peking University Peoples Hospital, Beijing 100044, China.
Center of Gynecologic Oncology, Peking University Peoples Hospital, Beijing 100044, China.
Chin Med J (Engl). 2020 Jun 5;133(11):1285-1291. doi: 10.1097/CM9.0000000000000785.
Human epididymis secretory protein 4 (HE4) is a new ovarian cancer biomarker. The factors influencing HE4 levels are not clear, and the reference data in China are limited. Here, we aim to evaluate the effects of menopause and age on HE4 levels and to provide a possible reference value for HE4 in healthy Chinese people.
A total of 2493 healthy females aged 40 years or older were recruited from March 2013 to March 2017 with the cooperation of four medical institutions across Beijing, China. The serum levels of HE4 and cancer antigen 125 (CA125) were measured by enzyme-linked immunosorbent assay. The Wilcoxon rank-sum test of variance and a stratified analysis were used to analyze the relationships among age, menopausal status, and levels of HE4 or CA125. Confidence intervals (5%-95%) were determined for reference ranges in different populations.
There was a statistically significant difference in median HE4 levels between the post-menopausal (n = 2168) and pre-menopausal groups (n = 325) (36.46 vs. 24.04 pmol/L, Z = -14.41, P < 0.001). HE4 increased significantly with age in the post-menopausal groups (H = 408.18, P < 0.001) but not in the pre-menopausal subjects (Z = -0.43, P = 0.67). The upper 95th percentile of HE4 levels were 44.63 pmol/L for pre-menopausal women, 78.17 pmol/L for post-menopausal women, and 73.3 pmol/L for all women. In the post-menopausal population, the HE4 reference ranges were 13.15 to 47.31, 14.31 to 58.04, 17.06 to 73.51, 24.50 to 115.25, and 35.71 to 212.37 pmol/L for different age groups from forty divided by decade. The CA125 level was affected mainly by menopausal status and not age.
Menopausal status and age were both important factors influencing the level of HE4, and age affected HE4 levels mainly in post-menopausal women. The HE4 level was higher in the post-menopausal population than in the pre-menopausal population and increased with age.
人附睾分泌蛋白4（HE4）是一种新型卵巢癌生物标志物。影响HE4水平的因素尚不清楚，且中国的参考数据有限。在此，我们旨在评估绝经和年龄对HE4水平的影响，并为中国健康人群的HE4提供可能的参考值。
2013年3月至2017年3月期间，在中国北京的四家医疗机构合作下，共招募了2493名40岁及以上的健康女性。采用酶联免疫吸附测定法检测血清HE4和癌抗原125（CA125）水平。采用方差的Wilcoxon秩和检验和分层分析来分析年龄、绝经状态与HE4或CA125水平之间的关系。确定不同人群参考范围的置信区间（5%-95%）。
绝经后组（n = 2168）和绝经前组（n = 325）的HE4中位数水平存在统计学显著差异（36.46对24.04 pmol/L，Z = -14.41，P < 0.001）。绝经后组中HE4随年龄显著增加（H = 408.18，P < 0.001），而绝经前受试者中则无此现象（Z = -0.43，P = 0.67）。绝经前女性HE4水平的第95百分位数为44.63 pmol/L，绝经后女性为78.17 pmol/L，所有女性为73.3 pmol/L。在绝经后人群中，按每十岁划分的不同年龄组的HE4参考范围分别为13.15至47.31、14.31至58.04、17.06至73.51、24.50至115.25和35.71至212.37 pmol/L。CA125水平主要受绝经状态影响，而非年龄。
绝经状态和年龄都是影响HE4水平的重要因素，年龄主要影响绝经后女性的HE4水平。绝经后人群的HE4水平高于绝经前人群，且随年龄增加。
