乳腺癌患者血液中PGRMC1浓度与临床相关性

doi:10.3969/j.issn.1006-7795.2018.04.002

首都医科大学学报 ›› 2018, Vol. 39 ›› Issue (4): 486-493.doi: 10.3969/j.issn.1006-7795.2018.04.002

乳腺癌患者血液中PGRMC1浓度与临床相关性

赵越¹, 阮祥燕^1,2, 张泉东³, 王虎生¹, 李雪¹, 蔡桂举¹, 谷牧青¹, Alfred O. Mueck^1,2

1. 首都医科大学附属北京妇产医院内分泌科, 北京 100026;
2. 德国图宾根大学妇产医院妇女健康部与妇女健康研究中心, 图宾根 D-72076, 德国;
3. 解放军263医院外科, 北京 101149

收稿日期:2018-05-31 出版日期:2018-07-21 发布日期:2018-07-21
通讯作者: 阮祥燕 E-mail:ruanxiangyan@163.com
基金资助:
国家自然科学基金（81671411），北京市自然科学基金（7162062），北京市医院管理局"登峰"计划专项经费资助（DFL20181401），北京市卫生系统高层次卫生技术人才（学科带头人）（2014-2-016），首都医科大学附属北京妇产医院，北京妇幼保健院学科带头人项目（2013-1）。

Correlation between the blood membrane-bound progesterone level and clinical application in patients with breast cancer

Zhao Yue¹, Ruan Xiangyan^1,2, Zhang Quandong³, Wang Husheng¹, Li Xue¹, Cai Guiju¹, Gu Muqing¹, Alfred O. Mueck^1,2

1. Department of Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China;
2. Department for Women's Health, University Women's Hospital and Research Center for Women's Health, University of Tuebingen, Tuebingen D-72076, Germany;
3. Department of Surgery, the 263 th Hospital of People's Liberation Army, Beijing 101149, China

Received:2018-05-31 Online:2018-07-21 Published:2018-07-21
Supported by:
This study was supported by National Natural Science Foundation of China (81671411); Natural Science Foundation of Beijing (7162062); Beijing Municipal Administration of Hospitals ‘Ascent’ Plan (DFL20181401); Beijing Municipality Health Technology High-level Talent (2014-2-016); Project of Discipline Leader, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital(2013-1).

摘要/Abstract

摘要： 目的本研究通过检测乳腺癌患者血液中孕激素受体膜组分1（progesterone receptor membrane component 1，PGRMC1）表达浓度来评价其在乳腺癌诊断中的临床价值。方法选取2016年9月至2018年1月期间因乳腺疾病就诊于首都医科大学附属北京妇产医院乳腺外科、中国医学科学院肿瘤医院乳腺外科以及解放军263医院乳腺外科的患者140例，检测其血清及全血标本，其中乳腺癌组90例。根据临床分期早期50例：Ⅰ期（n=24）、Ⅱ期（n=26），晚期40例：Ⅲ期（n=20）、Ⅳ期（n=20）。乳腺良性肿瘤组50例。采用数字表法随机抽取同期门诊健康体检者30例作为对照组。全血样本处理后采用酶联免疫吸附剂测定法（enzyme linked immunosorbent assay，ELISA）测定各组PGRMC1浓度，化学发光免疫分析法（chemiluminescent immunoassay，CLIA）测定各组血清CA125、CA153和CEA表达浓度。ROC曲线评价PGRMC1在乳腺癌诊断中的应用价值。结果 PGRMC1浓度在乳腺癌、乳腺良性疾病患者及正常对照人群中差异有统计学意义（P=0.000）。乳腺癌患者中PGRMC1浓度随临床分期增加而逐渐升高，明显高于乳腺良性疾病组及对照组浓度[Ⅱ期（60.89 ±16.86）ng/L，Ⅲ期（95.54 ±16.79）ng/L，Ⅳ期（113.78 ±41.20）ng/L vs良性肿瘤组（42.77 ±29.81）ng/L，对照组（39.36 ±25.10）ng/L]，组间比较差异有统计学意义（P<0.05）。与乳腺良性疾病组与正常对照组相比，乳腺癌晚期组3种肿瘤标志物明显升高（Ⅲ期：CA125：χ²=12.26，P=0.000；CA153：χ²=28.19，P=0.000；CEA：χ²=6.52，P=0.011；Ⅳ期：CA125：χ²=16.46，P=0.000；χ²=42.19，P=0.000；CEA：χ²=14.29，P=0.000）。与乳腺癌早期组比较，差异无统计学意义（P>0.05）；乳腺良性疾病组与正常组比较，差异无统计学意义（P>0.05）。受试者工作特征（receiver operating characteristic，ROC）曲线分析显示晚期组PGRMC1的曲线下面积（area under the ROC，AUC）为82.7%（P<0.05），CA125、CA153、CEA的AUC分别为78.3%（P<0.05）、86.8%（P<0.05）、77.3%（P<0.05）。早期组中，CA125、CA153和CEA的AUC均小于60%（P>0.05）。而PGRMC1的AUC为86.6%（P<0.05），敏感度为94.0%，特异度为50.0%。结论乳腺癌患者全血中PGRMC1表达含量高，且表达程度随乳腺癌期别的增加而增高；PGRMC1对早晚期乳腺癌诊断均有一定的临床参考价值，有望成为激素治疗前乳腺癌风险常规筛查的血液学标志物。

关键词: 绝经激素治疗, 孕激素受体膜组分1, 乳腺癌, 酶联免疫吸附测定, 血液生物学标志物, 受试者工作特征曲线

Abstract: Objective To detect the PGRMC1 level in blood samples from breast cancer patients and evaluate the clinical value in diagnosis of breast cancer. Methods The whole blood PGRMC1 levels were measured by enzyme linked immunosorbent assay (ELISA) and the serum CA125, CEA and CA153 levels were measured by chemiluminescent immunoassay (CLIA) technique in 90 breast cancer patients, 50 breast benign diseases and 30 healthy controls from September 2017 to January 2018. All participants signed informed consent voluntarily. Chi-square test was used for comparison between groups. Receiver operating characteristic (ROC) curve was used to evaluate diagnosis value of PGRMC1 in breast cancer. Results The level of PGRMC1 showed no difference between the benign group and the control group (P>0.05). The PGRMC1 levels showed significant difference in stage Ⅱ, Ⅲ and IV breast cancer group compared with the benign and the control groups (P<0.05 compared among groups). There was no significant change in the serum levels of CA125, CA153 and CEA in stage I and Ⅱ breast cancer patients with no statistically significant difference compared with the benign group and the control group (P>0.05). Compared with the benign group and the control group, the serum value of CA125, CA153 and CEA was significantly higher in stage Ⅲ and IV breast cancer group (P<0.05). In late stage, the area under the ROC curve (AUC) of PGRMC1, CA125, CA153 and CEA was 82.7%, 78.3%, 86.8% and 77.3% respectively. In early stage, the AUC of CA125, CA153 and CEA was below 60%, which showed nearly no significance in diagnosis for early breast cancer. While the AUC of PGRMC1 was 86.6%. The sensitivity of PGRMC1 was 94% and the specificity was 50%. Conclusion PGRMC1 was successfully detected with ELISA in blood samples from breast cancer patients and had applicable value for diagnosis in both early and late phase of breast cancer. There is a possibility that PGRMC1 may become a blood biomarker of early diagnosis and progression of breast cancer.

Key words: menopausal hormone therapy, progesterone receptor membrane component 1, breast cancer, enzyme-linked immuno sorbent assay, biomarker, receiver operating characteristic curve

中图分类号:

R711.77

赵越, 阮祥燕, 张泉东, 王虎生, 李雪, 蔡桂举, 谷牧青, Alfred O. Mueck. 乳腺癌患者血液中PGRMC1浓度与临床相关性[J]. 首都医科大学学报, 2018, 39(4): 486-493.

Zhao Yue, Ruan Xiangyan, Zhang Quandong, Wang Husheng, Li Xue, Cai Guiju, Gu Muqing, Alfred O. Mueck. Correlation between the blood membrane-bound progesterone level and clinical application in patients with breast cancer[J]. Journal of Capital Medical University, 2018, 39(4): 486-493.

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乳腺癌患者血液中PGRMC1浓度与临床相关性

Correlation between the blood membrane-bound progesterone level and clinical application in patients with breast cancer

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