乳腺癌细胞缺氧微环境中癌胚抗原的表达及其对预后的判断意义  

The expression level of carcinoembryonic antigen under hypoxic condition in breast cancer ;microenvironment and its prognostic value of breast cancer

作　　者：任丽[1] 柳雅慧 夏文超[3] 黄琛[3] 葛洁[2] 

机构地区：[1]天津医科大学肿瘤医院检验科国家肿瘤临床医学研究中心乳腺癌防治教育部重点实验室天津市肿瘤防治重点实验室天津市恶性肿瘤临床医学研究中心,300060 [2]天津医科大学肿瘤医院乳腺肿瘤一科,300060 [3]天津医科大学

出　　处：《中华检验医学杂志》2016年第9期710-714,共5页Chinese Journal of Laboratory Medicine

基　　金：国家自然科学基金（81402174）

摘　　要：目的：探究癌胚抗原（ CEA）表达水平与乳腺癌缺氧微环境的关系及其预后价值。方法横断面调查。在缺氧和常氧条件下培养乳腺癌细胞 MDA-MB-231，采用蛋白免疫印迹法（ Western blotting）检测其CEA的表达变化；收集天津医科大学肿瘤医院2013年4月至2015年6月30例乳腺浸润性癌标本，采用免疫组织化学染色法检测乳腺癌病理组织中CEA﹑缺氧诱导因子-1α（ HIF-1α）和碳酸酐酶-9（ CA-9）的表达水平；收集我院2009年4月至2011年6月166例乳腺癌患者术前血清，采用电化学发光法检测血清CEA水平，同时采用Logistic单因素分析法研究患者临床资料与CEA水平的相关性；采用Kaplan-Meier法计算乳腺癌患者无进展生存期，Log-rank法比较组间差异。结果乳腺癌细胞缺氧条件下CEA蛋白水平明显高于常氧条件，且CEA蛋白水平随着缺氧时间的延长而升高；乳腺癌病理组织免疫组织化学染色结果显示，HIF-1α表达区域可见CEA高表达， CEA与CA-9在同一区域共同表达，线性回归法分析发现CEA表达水平与HIF-1α（ P＝0.0096）的表达水平具有相关性；术前升高的血清CEA水平与患者肿瘤长径大小密切相关（ P＝0.015）﹑淋巴结转移密切相关（ P＝0.032）；乳腺癌患者CEA阳性组和CEA阴性组无进展生存期分别为29.85个月和39.08个月，差异有统计学意义（ P＝0.003）。结论 CEA在乳腺癌缺氧微环境中表达上调，血清CEA水平可以作为乳腺癌患者预后的评价指标。Objective To investigate the correlationbetween thecarcinoembryonic antigen （ CEA） level and hypoxic status of breast cancer, and itspotential of being a prognostic factor in breast cancer. Methods Breast cancer cell line MDA-MB-231 was cultured under hypoxic or normoxic condition to determine the protein level of CEA using Western blotting.30 breast cancer tissue sections were collected in Tianjin Medical University Cancer Institute and Hospital from April 2013 to June 2015.and were detected the expression of CEA, hypoxia-inducible factor-1α（ HIF-1α） and carbonic anhydrase-9 （ CA-9 ） by immunohistochemistry.Serum CEA were detected by immunofluorescence assay of 166 breast cancer patients collected from April 2009 to June 2011.The correlation between the expression levels of CEA and breast cancer patients＆#39;clinical data was analyzed by Logistic univariate analysis.Kaplan-Meier method was employed to calculate the progression-free survival of patients with breast cancer. Log-rank test was conducted to compare the difference between groups.Results CEA levels were significantly higher in breast cancer cells under hypoxic condition in a time-dependent manner, compared to normoxiccontrol. Immunohistochemical staining indicated that CEA was coexpressed with HIF-1αand CA-9 in breast cancer and linear regression analysis revealed that CEA expression correlated with HIF-1α（ P =0.0096 ）;Preoperative serum levels of CEA were closely related with tumor size （ P =0.015 ） andLymph node metastasis（P=0.032）; CEA positive patients achieved a progression-free survival of 29.85months（versus 39.08 months in CEA negative patients, P=0.003）.Conclusions Hypoxia upregulates CEA expression in breast cancer and the levels of preoperative serum CEA is a potential prognostic factor ofbreast cancer.

关 键 词：乳腺癌 癌胚抗原 缺氧微环境 预后 

分 类 号：R737.9[医药卫生—肿瘤]