南方医科大学学报

南方医科大学学报 ›› 2021, Vol. 41 ›› Issue (10): 1456-1463.doi: 10.12122/j.issn.1673-4254.2021.10.03

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中国女性外周血EMR3基因甲基化水平与乳腺癌的相关性

周夏婕，雷水芳，黎立喜，徐 天，顾万建，马 飞，杨蓉西   

  1. 南京医科大学公共卫生学院流行病与卫生统计学系，江苏 南京 211166；国家癌症中心//国家肿瘤临床医学研究中心//中国医学科学院北京协和医学院肿瘤医院肿瘤内科，北京 100021；江苏省中医院检验科，江苏 南京 210029
  • 出版日期:2021-10-20 发布日期:2021-11-11

Peripheral blood EMR3 gene methylation level is correlated with breast cancer in Chinese women

ZHOU Xiajie, LEI Shuifang, LI Lixi, XU Tian, GU Wanjian, MA Fei, YANG Rongxi   

  1. Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China; Department of Clinical Laboratory, Jiangsu Provincial Hospital of Chinese Medicine, Nanjing 210029, China
  • Online:2021-10-20 Published:2021-11-11

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摘要： 目的 探究中国人群外周血中C19orf57、MAP9、EMR3、NEK6和PCOLCE2基因的甲基化水平与乳腺癌的相关性。方法 通过病例对照研究收集了258例早期乳腺癌患者和272名健康女性的外周血，并采用基质辅助激光解吸电离飞行时间质谱技术（MALDI-TOF-MS）定量检测基因上CpG位点的甲基化水平。使用logistics回归模型校正协变量分析DNA甲基化水平与乳腺癌的相关性。Spearman秩相关用于分析基因甲基化水平与年龄的关系。使用非参数检验分析不同临床特征组别的甲基化水平差异。结果 与欧美人群的乳腺癌EMR3高甲基化相反，EMR3基因的低甲基化与中国女性的乳腺癌相关，但该相关性仅存在于≥ 50 岁的女性中（每减少 10%的甲基化，EMR3_CpG_1：OR=1.40；EMR3_CpG_2：OR=2.31；EMR3_CpG_3：OR=2.76，P< 0.05）。EMR3的甲基化水平与肿瘤分期、大小、淋巴转移、ER、PR、HER2、Ki67等没有或仅有弱相关。C19orf57甲基化与乳腺癌无相关性。结论 外周血EMR3基因的低甲基化与中国女性乳腺癌之间存在相关性，尤其是年龄较大或绝经后女性。

关键词: 外周血, EMR3, DNA甲基化, 乳腺癌, 质辅助激光解吸电离飞行时间质谱技术

Abstract: Objective To explore the association of methylation levels of C19orf57, MAP9, EMR3, NEK6 and PCOLCE2 genes in peripheral blood with breast cancer (BC) in Chinese women. Methods We collected peripheral blood samples from 258 early-stage BC patients and 272 healthy women. Agena matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was utilized to quantitatively measure the methylation levels of CpG sites in the genes. The association between DNA methylation and BC was analyzed using a logistic regression model adjusted for covariants. Spearman's correlation analysis was performed to analyze the association between the gene methylation levels and age. The methylation levels of the genes in the BC patients with different clinical characteristics were investigated using non-parametric tests. Results In stead of EMR3 gene hypermethylation as found in BC patients as found in the Caucasian population, EMR3 gene hypomethylation was found to correlate with BC in Chinese women, but this correlation was significant only in women beyond the age of 50 years (for every 10% reduction of the methylation level, EMR3_CpG_1: OR=1.40; EMR3_CpG_2: OR=2.31; EMR3_CpG_3: OR=2.76, P<0.05). EMR3 methylation was not or was only weakly correlated with tumor stage, size, lymphatic metastasis, ER, PR, HER2, or Ki67. Our data did not show a correlation between C19orf57 methylation and BC. Conclusion Peripheral blood EMR3 gene hypomethylation is associated with BC in Chinese women, especially in those at an old age and in postmenopausal women.

Key words: peripheral blood, EMR3, DNA methylation, breast cancer, MALDI-TOF