mRNA and microRNA Expression Profiles in Circulating Tumor Cells and Primary Tumors of Metastatic Breast Cancer Patients
mRNA and microRNA Expression Profiles in Circulating Tumor Cells and Primary Tumors of Metastatic Breast Cancer Patients
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DOI：
10.1158/1078-0432.ccr-11-0255
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发表时间：
2011-06-01
影响因子：
11.5
通讯作者：
Martens, John W. M.
中科院分区：
文献类型：
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作者：
Sieuwerts, Anieta M.;Mostert, Bianca;Martens, John W. M.
目的：循环肿瘤细胞（CTC）的分子表征具有广阔的应用前景。不幸的是，常规分离的CTC组分目前仍含有污染的白细胞，这使得CTC特异性分子表征极具挑战性。在这项研究中，我们检测了被认为与乳腺癌临床相关的潜在ctc特异性基因的mRNA和microRNA （miRNA）表达。实验设计：使用基于上皮细胞粘附分子的CellSearch Profile Kit分离ctc。在53名健康献血者（HBD）和8名原发肿瘤患者的血液中，在开始一线全身治疗前收集的50名转移性乳腺癌患者的ctc中，通过实时逆转录酶PCR检测选定的基因。分子谱与CTC计数和临床参数相关，并与相应原发肿瘤产生的谱进行比较。结果：我们在32例至少有5个ctc的患者的7.5 mL血液样本中鉴定出55个mrna和10个miRNAs，与9例未检测到ctc和HBDs的患者的样本相比，这些样本中表达更丰富。聚类分析得到4个不同的患者聚类，其特征为5个不同的基因簇。从第2组到第4组的患者中有两倍的患者发生了内脏和非内脏转移。将ctc中的转录物水平与相应原发肿瘤中的转录物水平进行比较，发现雌激素受体和HER2水平存在临床相关差异。结论：我们的研究表明，在高白细胞背景下对低数量的CTCs进行分子分析是可行的，并为进一步研究CTCs分子特征的临床相关性提供了希望。临床癌症研究；17 (11);3600 - 18。AACR (C) 2011。
Purpose: Molecular characterization of circulating tumor cells (CTC) holds great promise. Unfortunately, routinely isolated CTC fractions currently still contain contaminating leukocytes, which makes CTC-specific molecular characterization extremely challenging. In this study, we determined mRNA and microRNA (miRNA) expression of potentially CTC-specific genes that are considered to be clinically relevant in breast cancer.Experimental Design: CTCs were isolated with the epithelial cell adhesion molecule-based CellSearch Profile Kit. Selected genes were measured by real-time reverse transcriptase PCR in CTCs of 50 metastatic breast cancer patients collected before starting first-line systemic therapy in blood from 53 healthy blood donors (HBD) and in primary tumors of 8 of the patients. The molecular profiles were associated with CTC counts and clinical parameters and compared with the profiles generated from the corresponding primary tumors.Results: We identified 55 mRNAs and 10 miRNAs more abundantly expressed in samples from 32 patients with at least 5 CTCs in 7.5 mL of blood compared with samples from 9 patients without detectable CTCs and HBDs. Clustering analysis resulted in 4 different patient clusters characterized by 5 distinct gene clusters. Twice the number of patients from cluster 2 to 4 had developed both visceral and nonvisceral metastases. Comparing transcript levels in CTCs with those measured in corresponding primary tumors showed clinically relevant discrepancies in estrogen receptor and HER2 levels.Conclusions: Our study shows that molecular profiling of low numbers of CTCs in a high background of leukocytes is feasible and shows promise for further studies on the clinical relevance of molecular characterization of CTCs. Clin Cancer Res; 17(11); 3600-18. (C)2011 AACR.