Messenger RNA expression levels of CXCR4 correlate with metastatic behavior and outcome in patients with osteosarcoma
Messenger RNA expression levels of CXCR4 correlate with metastatic behavior and outcome in patients with osteosarcoma
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DOI：
10.1158/1078-0432.ccr-04-1089
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发表时间：
2005-04-01
影响因子：
11.5
通讯作者：
Gorlick, R
中科院分区：
文献类型：
--
作者：
Laverdiere, C;Hoang, BH;Gorlick, R
目的：为了确定骨肉瘤细胞是否表达趋化因子受体，以及它们的存在或不存在是否与临床特征有关，实验设计：采用荧光定量实时PCR，分析了3种骨肉瘤细胞系和68例骨肉瘤患者样本中17种趋化因子受体的模式。在高级别骨肉瘤患者样本（n = 47）中，CXCR 4是最常见的表达（63%），其表达水平与总生存期（P < 0.0001）、无事件生存期（P < 0.001）和无转移生存期（MFS; P = 0.002）呈负相关。CXCR 4表达水平与诊断时有无转移也有相关性（P = 0.002）。CCR 7在43%的样本中表达，其表达水平与总生存率（P = 0.03）和MFS（P = 0.007）呈负相关。CCR 10 mRNA表达水平与MFS呈负相关（P = 0.009）。CXCR 4、CCR 7和CCR 10的表达之间没有关联。在研究基质细胞衍生因子-1表达的26个样本中，77%表达了它，但与临床变量或CXCR 4表达无关。多因素分析显示CXCR 4 mRNA表达水平是影响骨肉瘤患者总生存期（P = 0.0006）、无事件生存期（P = 0.004）和MFS（P = 0.025）的唯一显著变量。如果进一步的研究证实它与这种疾病的转移有关，它可能代表一个新的治疗靶点。
Purpose: To determine if osteosarcoma cells express chemokine receptors and if their presence or absence relates to clinical features.Experimental Design: Using fluorescent quantitative real-time PCR, the pattern of 17 chemokine receptors in 3 osteosarcoma cell lines and 68 osteosarcoma patient samples was analyzed.Results: The expression of the chemokine receptors was generally low among the cell lines. In the high-grade osteosarcoma patient samples (n = 47), CXCR4 was the most commonly expressed (63%) and its expression level was inversely correlated to overall survival (P < 0.0001), event-free survival (P < 0.001), and metastasis-free survival (MFS; P = 0.002). There was also a correlation between the expression level of CXCR4 and the presence of metastasis at diagnosis (P = 0.002). CCR7 was expressed in 43% of the samples and its expression level was inversely correlated with overall survival (P = 0.03) and MFS (P = 0.007). CCR10 mRNA expression level was inversely correlated with MFS (P = 0.009). There was no association between the expression of CXCR4, CCR7, and CCR10. Of the 26 samples studied for stromal cell-derived factor-1 expression, 77% expressed it, but there was no correlation with the clinical variables or CXCR4 expression. Multivariate analysis revealed that mRNA expression level of CXCR4 was the only significant variable for overall survival (P = 0.0006), event-free survival (P = 0.004), and MFS (P = 0.025).Conclusions: These data suggest that CXCR4 could be useful as a prognostic factor and as a predictor of potential metastatic development in osteosarcoma. If further studies confirm that it is relevant to metastases in this disease, it could represent a new therapeutic target.