Chemokine receptor CXCR4 expression is correlated with VEGF expression and poor survival in soft-tissue sarcoma
Chemokine receptor CXCR4 expression is correlated with VEGF expression and poor survival in soft-tissue sarcoma
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DOI：
10.1002/ijc.24128
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发表时间：
2009-04-15
影响因子：
6.4
通讯作者：
Tsuneyoshi, Masazumi
中科院分区：
文献类型：
--
作者：
Oda, Yoshinao;Tateishi, Naomi;Tsuneyoshi, Masazumi
趋化因子受体 CXCR4 的表达与多种人类恶性肿瘤的不良预后和 VEGF 表达相关。我们测量了软组织肉瘤中 CXCR4 的表达水平，并将其与 VEGF 表达或微血管密度 (MVD) 进行比较。我们使用实时定量PCR检测了总共176个肿瘤中CXCR4和VEGF的表达水平，其中包括24个中间肿瘤、24个恶性圆细胞肿瘤（MRCT）和128个恶性非圆细胞肿瘤（MNRCT）。我们还评估了它们的 CXCR4 和 VEGF 的免疫组织化学表达、MVD 和增殖活性（通过 MIB-1 标记指数 (LI) 测量）。此外，我们使用 Cox 回归模型评估了它们对于 MNRCT 中患者生存率的显着性。在不同类型的肿瘤组织中，MNRCT 中 CXCR4 (p < 0.0001) 和 VEGF (p < 0.0001) 的表达水平显着高于中间肿瘤或 MRCT。 CXCR4和VEGF的免疫组织化学表达水平与其mRNA表达水平显着相关(p < 0.0001)。在 112 个原发性 MNRCT 中发现 CXCR4 和 VEGF 表达之间存在显着正相关（r = 0.434，p < 0.0001）。此外，单变量（p < 0.0001）和 Cox 多变量分析（p = 0.0001）均显示，除了美国癌症联合委员会的高分期和高 MIB-1-LI 之外，CXCR4 的过度表达是一个独立的不良预后因素。确定CXCR4表达水平作为一种新的标志物可以为患者提供有用的预后信息，并且它可以成为软组织肉瘤MNRCT分子靶向治疗的候选者。 (C) 2008 Wiley-Liss, Inc.
The expression of chemokine receptor CXCR4 has been associated with poor prognosis and VEGF expression in several kinds of human malignancy. We measured CXCR4 expression levels in soft-tissue sarcoma and compared them with VEGF expression or microvessel density (MVD). We used real-time quantitative PCR to examine the CXCR4 and VEGF expression levels in a total 176 tumors, including 24 intermediate tumors, 24 malignant round-cell tumors (MRCTs) and 128 malignant non-round-cell tumors (MNRCTs). We also assessed their immunohistochemical expression of CXCR4 and VEGF, MVD and proliferative activities, as measured by the MIB-1-labeling index (LI). Furthermore, we evaluated their significance with respect to patient survival rates in MNRCTs, using the Cox regression model. Within the different types of tumor tissue, the expression levels of CXCR4 (p < 0.0001) and VEGF (p < 0.0001) in MNRCTs were significantly higher than those in intermediate tumors or MRCTs. Immunohistochemical expression levels of CXCR4 and VEGF were significantly correlated with their mRNA expression levels (p < 0.0001). Significant positive correlation was found between CXCR4 and VEGF expression in 112 primary MNRCTs (r = 0.434, p < 0.0001). Moreover, both univariate (p < 0.0001) and Cox multivariate analysis (p = 0.0001) revealed that overexpression of CXCR4 was an independent adverse prognostic factor, in addition to high stage according to the American Joint Committee on Cancer and a high MIB-1-LI. Determination of the CXCR4 expression level as a novel marker can provide useful prognostic information for patients and it could be a candidate for molecular targeting therapy in MNRCTs of soft-tissue sarcomas. (C) 2008 Wiley-Liss, Inc.