间接法建立上海地区成年人血清CA50的参考区间

doi:10.3969/j.issn.1673-8640.2025.11.005

摘要/Abstract

摘要：

目的采用间接法（Hoffmann法）建立上海地区成人糖类抗原50（CA50）的参考区间并验证其适用性。方法收集2022年8月—2023年7月复旦大学附属中山医院实验室信息管理系统中46 764例CA50的原始检测数据，用于参考区间的建立。选取2024年1—3月复旦大学附属中山医院表观健康体检者691名，用于自建参考区间的验证。另选取2022年8月—2024年3月复旦大学附属中山医院体检人群中CA50≥25 U·mL^-1（现用参考区间）同时又低于自建参考区间的体检者，用于验证自建参考区间的适用性。采用Turkey法剔除离群值。采用Z检验比较不同性别和年龄的研究对象CA50水平是否存在差异。采用Hoffmann法建立血清CA50的95%参考区间。结果筛选后得到17 773例有效数据。Z检验结果显示，不同性别和年龄的CA50水平差异均有统计学意义（Z值>Z*值）。采用Hoffmann法依据年龄和性别分别建立CA50的95%参考区间，其中18~59岁男性为<27.30 U·mL^-1、18~59岁女性为<29.62 U·mL^-1、≥60岁男性为<36.85 U·mL^-1、≥60岁女性为<34.85 U·mL^-1。691名表观健康体检者的CA50水平均在自建参考区间范围内，参考区间验证通过。191名CA50≥25 U·mL^-1（现用参考区间）同时又低于自建参考区间的体检者中有38名（19.90%）存在肝功能、肾功能、B超或电子计算机断层扫描（CT）结果异常，其他153名（80.10%）体检者检查结果均正常。结论采用Hoffmann法建立了上海地区成人CA50不同性别和年龄的参考区间，与现用参考区间存在一定的差异，更适用于临床。

关键词: 糖类抗原50, 间接法, 参考区间

Abstract:

Objective To establish the reference range of carbohydrate antigen 50 （CA50 ）for adults in Shanghai by indirect method （Hoffmann method） and verify its applicability. Methods The 46 764 cases of original CA50 determination data in the laboratory information management system of Zhongshan Hospital of Fudan University from August 2022 to July 2023 were collected for the establishment of CA50 reference range. Totally，691 healthy subjects at Zhongshan Hospital of Fudan University from January to March 2024 were enrolled for the verification of the self-established reference range. The individuals from the physical examination population of Zhongshan Hospital of Fudan University from August 2022 to March 2024 with CA50≥25 U·mL^-1（current reference range）but lower than the self-established reference range were selected to verify the applicability of the self-established reference range. Turkey method was used to eliminate outliers. Z test was used to compare whether there were differences in CA50 levels among different genders and ages. The 95% reference range of serum CA50 was established using the Hoffmann method. Results Totally，17 773 valid data were obtained. The Z test results showed that there was statistical significance in CA50 levels among different genders and ages（Z value > Z* value）. The 95% reference ranges of CA50 were established for different genders and ages using the Hoffmann method. That for male individuals aged 18-59 years was <27.30 U·mL^-1，and that for female individuals was <29.62 U·mL^-1. That for male aged ≥60 years was <36.85 U·mL^-1，and that for female individuals was <34.85 U·mL^-1. The CA50 levels of 691 healthy individuals were within the self-established reference range，and the reference range verification was successful. Among the 191 individuals with CA50≥25 U·mL^-1（current reference range）and lower than the self-established reference range，38（19.90%）individuals had abnormal liver function，renal function，B-ultrasound or computed tomography（CT）results，while the other 153 （80.10%） individuals had normal examination results. Conclusions The Hoffmann method has established the reference range of CA50 for adults in Shanghai by gender and age，which is different from the current reference range and is more applicable in clinical practice.

Key words: Carbohydrate antigen 50, Indirect method, Reference range

中图分类号:

R446.1

潘亚芳, 朱晶, 邵文琦, 杨静, 潘柏申, 王蓓丽, 郭玮. 间接法建立上海地区成年人血清CA50的参考区间[J]. 检验医学, 2025, 40(11): 1059-1063.

PAN Yafang, ZHU Jing, SHAO Wenqi, YANG Jing, PAN Baishen, WANG Beili, GUO Wei. Establishment of reference range of serum CA50 for adults in Shanghai by indirect method[J]. Laboratory Medicine, 2025, 40(11): 1059-1063.

图/表 5

参考文献 14

[1]	NILSSON O, MÅNSSON J E, LINDHOLM L, et al. Sialosyllactotetraosylceramide,a novel ganglioside antigen detected in human carcinomas by a monoclonal antibody[J]. FEBS Lett, 1985, 182(2):398-402. DOI URL
[2]	TAO L Y, CAI L, HE X D, et al. Comparison of serum tumor markers for intrahepatic cholangiocarcinoma and hepatocellular carcinoma[J]. Am Surg, 2010, 76(11):1210-1213.
[3]	SHAN M, TIAN Q, ZHANG L. Serum CA50 levels in patients with cancers and other diseases[J]. Prog Mol Biol Transl Sci, 2019,162:187-198.
[4]	PRETORIUS C J, TATE J R, WILGEN U, et al. A critical evaluation of the Beckman Coulter Access hsTnI:analytical performance,reference interval and concordance[J]. Clin Biochem, 2018,55:49-55.
[5]	JONES G R D, HAECKEL R, LOH T P, et al. Indirect methods for reference interval determination-review and recommendations[J]. Clin Chem Lab Med, 2018, 57(1):20-29. DOI URL
[6]	HOFFMANN R G. Statistics in the practice of medicine[J]. JAMA, 1963,185:864-873.
[7]	中华人民共和国国家卫生健康委员会.WS/T 402—2024 临床实验室定量检验项目参考区间的制定[S]. 北京: 中华人民共和国国家卫生健康委员会, 2024.
[8]	HORN P S, FENG L, LI Y, et al. Effect of outliers and nonhealthy individuals on reference interval estimation[J]. Clin Chem, 2001, 47(12):2137-2145. PMID
[9]	LIAO Q, ZHAO Y P, YANG Y C, et al. Combined detection of serum tumor markers for differential diagnosis of solid lesions located at the pancreatic head[J]. Hepatobiliary Pancreat Dis Int, 2007, 6(6):641-645.
[10]	LUCAROTTI M E, HABIB N A, KELLY S B, et al. Clinical evaluation of combined use of CEA,CA19-9 and CA50 in the serum of patients with pancreatic carcinoma[J]. Eur J Surg Oncol, 1991, 17(1):51-53.
[11]	Clinical and Laboratory Standards Institute. Defining,establishing,and verifying reference intervals in the clinical laboratory;approved guideline-third edition[S]. EP28-A3c,CLSI, 2010.
[12]	HARRIS E K, BOYD J C. On dividing reference data into subgroups to produce separate reference ranges[J]. Clin Chem, 1990, 36(2):265-270. PMID
[13]	李响新, 刘德慧, 高永升, 等. 正常成人NSE、CA50和CA242参考区间的研究[J]. 标记免疫分析与临床, 2021, 28(6):1002-1006.
[14]	BUNCH D R, KOCH C D. Reference intervals:a Hoffmann method improvement?[J]. J Appl Lab Med, 2024, 9(2):197-200. DOI URL

组别	例数	CA50/（U·mL^-1）
男性组	9 022	1.31±0.17
女性组	8 751	1.39±0.20
Z值		28.69
Z*值		25.82

组别	例数	CA50/（U·mL^-1）
男性组	9 022	1.31±0.17
女性组	8 751	1.39±0.20
Z值		28.69
Z*值		25.82

组别	例数	CA50/（U·mL^-1）
18~59岁组	8 621	1.41±0.24
≥60岁组	9 152	1.54±0.29
Z值		32.63
Z*值		25.82

组别	例数	CA50/（U·mL^-1）
18~59岁组	8 621	1.41±0.24
≥60岁组	9 152	1.54±0.29
Z值		32.63
Z*值		25.82

项目	例数	CA50		参考区间（95%可信区间）/（U·mL^-1）
项目	例数	中位数/（U·mL^-1）	范围/（U·mL^-1）	参考区间（95%可信区间）/（U·mL^-1）
18~59岁
男性	4 080	5.45	3.26~9.64	<27.30（27.23~27.36）
女性	4 541	6.17	3.76~11.40	<29.62（28.86~30.38）
≥60岁
男性	4 942	7.56	4.64~13.32	<36.85（36.72~36.98）
女性	4 210	7.02	4.12~12.76	<34.85（34.72~34.98）