外周血癌细胞中多种肿瘤标记物基因检测预测乳腺癌患者转移和预后的意义

Significance of detection of multiple marker genes in cancer cells in peripheral blood in predication of metastases and prognosis of breast cancer patients

目的:筛选一组可检测乳腺癌循环癌细胞的标记物基因,分析乳腺癌患者相对循环癌细胞数(Lc)与临床病理特征的关联。方法:收集乳腺癌患者142例(乳腺癌组)和正常女性60人(正常对照组)外周血标本。利用CGAP提供的SAGE Genie数据库中数字基因表达演示工具,筛选一组可用于检测乳腺癌循环癌细胞的标记物基因(FAM83A、NPY1R和KRT19)。应用定量巢式PCR方法检测研究对象外周血中标记物基因的表达水平,并通过公式计算患者Lc值。结果:在乳腺癌组患者外周血中肿瘤标记物基因FAM83A、NPY1R和KRT19的表达水平均明显高于正常对照组(P<0.001)。142例乳腺癌患者中有113例(79.6%)至少表达1个肿瘤标记物基因。乳腺癌患者Lc值与其临床分期和远处转移有关联(P<0.001)。Kaplam-Meier生存曲线,Lc值小于2的患者生存时间明显长于Lc值大于2者(P=0.005)。结论:筛选了一组检测乳腺癌外周血循环癌细胞的标记物基因,联合该组基因计算的Lc值与患者临床分期和远处转移有关联,并可辅助判断乳腺癌预后。

Objective： To find a panel of marker genes for detection of circulating tumor cells of breast cancer,and to investigate the relationship between the relative cancer cell load （Lc） and the clinicopathological characteristics in the breast cancer patients.Methods： The peripheral blood samples from 142 breast cancer patients （breast cancer group） and 60 healthy female donors （normal control group） were collected.Digital Gene Expression Displayer Tool of the National Cancer Institute-Cancer Genome Anatomy Project was used to identify the marker genes for the detection of circulating tumor cells.Using real-time quantitative PCR method,the expression levels of a panel of marker genes （FAM83A,NPY1R and KRT19） in peripheral blood of the subjects were detected and the Lc value was calculated by the formula.Results： The expression levels of tumor marker genes （FAM83A,NPY1R and KRT19） in peripheral blood of the patients in breast cancer group were significantly higher than those in normal control group （P〈0.001）.In total,13 cases （79.6%） among the 142 breast cancer patient were found to express at least one tumor marker in blood samples.In addition,the Lc value was correlated with its clinical stage and distant metastasis in the breast cancer patients.The survival time of the breast cancer patients with Lc〉2 was shorter than that of the patients with Lc〈2.Conclusion： A novel panel of marker genes to detect the circulating tumor cells are identified.The Lc value calculated with these genes has relationship with the clinical stage and distant metastasis of the breast cancer patients and can be used to predict the prognosis of breast cancer.