Deregulated Serum Concentrations of Circulating Cell-Free MicroRNAs miR-17, miR-34a, miR-155, and miR-373 in Human Breast Cancer Development and Progression
Deregulated Serum Concentrations of Circulating Cell-Free MicroRNAs miR-17, miR-34a, miR-155, and miR-373 in Human Breast Cancer Development and Progression
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DOI：
10.1373/clinchem.2013.205161
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发表时间：
2013-10-01
影响因子：
9.3
通讯作者：
Schwarzenbach, Heidi
中科院分区：
文献类型：
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作者：
Eichelser, Corinna;Flesch-Janys, Dieter;Schwarzenbach, Heidi
背景：微小RNA（miRs）是一种小的非编码RNA，靶向参与肿瘤发生和进展的基因。在目前的研究中，我们研究了循环miR浓度作为乳腺癌患者血清中生物标志物的用途。我们分析了120例原发性乳腺癌患者手术后和化疗前的血清样本（M0，分为3个亚组，每组40例，分别为孕激素/雌激素阳性、HER 2阳性和三阴性癌症患者），32例明显转移患者（M1），40名健康女性使用定量TaqMan MicroRNA PCR，我们测量了已知与肿瘤发生和进展相关的6种循环microRNA（miR-10 b，-17，-34 a，-93，-155和-373）的相对浓度。这些数据与临床病理风险因素相关，特别是原发肿瘤的HER 2和激素受体状态以及转移的存在。循环miR-34 a的相对血清浓度[P = 0.013，曲线下面积（AUC）0.636]，miR-93（P = 0.001，AUC 0.699）和miR-373（P = 0.0001，AUC 0.879）在M0乳腺癌患者和健康女性之间存在显著差异，而miR-17 miR-155（P = 0.0001，AUC 0.781）在M0和M1患者之间表达不同。miR-373浓度增加与原发性肿瘤的阴性HER 2状态相关（P = 0.0001）。miR-17（P = 0.019）和miR-34 a（P = 0.029）的失调浓度分别在孕激素/雌激素受体阳性和阴性状态的患者中检测到。(c)2013年美国临床化学协会
BACKGROUND: MicroRNAs (miRs) are small, noncoding RNAs that target genes involved in tumor development and progression. In the current study, we investigated the use of circulating miR concentrations as biomarkers in the serum of breast cancer patients.METHODS: We analyzed serum samples from 120 patients with primary breast cancer after surgery and before chemotherapy (M0, classified into 3 subgroups of 40 patients with progesterone/estrogen-positive, HER2-positive, and triple-negative cancer), 32 patients with overt metastasis (M1), and 40 healthy women. Using quantitative TaqMan MicroRNA PCR, we measured the relative concentrations of 6 circulating microRNAs (miR-10b, -17, -34a, -93, -155, and -373) known to be relevant for tumor development and progression. The data were correlated with clinicopathologic risk factors, with particular reference to HER2 and hormone receptor status of the primary tumor and the presence of metastases.RESULTS: The relative serum concentrations of circulating miR-34a [P = 0.013, area under the curve (AUC) 0.636], miR-93 (P = 0.001, AUC 0.699), and miR-373 (P = 0.0001, AUC 0.879) were significantly different between M0 breast cancer patients and healthy women, whereas miR-17 (P = 0.002, AUC 0.679) and miR-155 (P = 0.0001, AUC 0.781) were differently expressed between M0 and M1 patients. Increased concentrations of miR-373 were associated with negative HER2 status of the primary tumor (P = 0.0001). Deregulated concentrations of miR-17 (P = 0.019) and miR-34a (P = 0.029) were detected in patients with progesterone/estrogen receptor-positive and -negative status, respectively.CONCLUSIONS: Our findings indicate that serum concentrations of deregulated microRNAs may be linked to a particular biology of breast carcinomas favoring progression and metastatic spread. (c) 2013 American Association for Clinical Chemistry