CD133 expression predicts lung metastasis and poor prognosis in osteosarcoma patients: A clinical and experimental study.

CD133 expression predicts lung metastasis and poor prognosis in osteosarcoma patients: A clinical and experimental study.
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CD133表达预测骨肉瘤患者的肺转移和不良预后:临床和实验研究

DOI:
10.3892/etm.2012.603
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发表时间:
2012-09
影响因子:
2.7
通讯作者:
Yao Y
Yao Y
中科院分区:
医学4区
文献类型:
--
作者:
He A;Qi W;Huang Y;Feng T;Chen J;Sun Y;Shen Z;Yao Y

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确定骨肉瘤(OS)的预后因素有助于选择需要更积极治疗的患者。已经发现CD 133是某些肿瘤类型的预后因子。然而,CD 133表达与OS预后之间的关系仍不清楚。在这项研究中,我们分析了CD 133在OS中的表达与临床因素和总生存期的关系,并进一步研究了其在体外转移中的潜在作用。CD 133阳性表达率为65.7%(46/70),与肺转移呈正相关(P=0.002),与Kaplan-Meier法计算的总生存期呈正相关(P=0.000)。多变量分析显示,CD 133表达是OS患者的独立预后因素。为了检测CD 133的直接参与,我们使用磁激活细胞分选法分离了MG 63细胞系中的CD 133+和CD 133 −细胞,发现与CD 133 −细胞相比,CD 133+细胞在划痕愈合试验中的迁移和Matrigel侵袭试验中的侵袭更活跃。逆转录-聚合酶链反应还发现CD 133+细胞中干性基因八聚体结合转录因子4(Oct-4)和NANOG以及转移相关受体C-X-C趋化因子受体4型(CXCR 4)的mRNA表达升高。因此,CD 133的表达与OS患者的肺转移和不良预后相关。CD 133+细胞可能是一种高表达自我更新能力和转移相关基因的肿瘤干细胞。
Identifying prognostic factors for osteosarcoma (OS) aids in the selection of patients who require more aggressive management. CD133 has been found to be a prognostic factor of certain tumor types. However, the association between CD133 expression and the prognosis of OS remains unknown. In this study, we analyzed the association of CD133 expression in OS with clinical factors and overall survival, and further investigated its potential role in metastasis in vitro. We found CD133 expression in 65.7% (46/70) of OS samples using immunohistochemistry, and it was positively correlated with lung metastasis analyzed by Chi-square test (P=0.002) and shorter overall survival time using the Kaplan-Meier method compared by log-rank test (P=0.000). Multivariate analysis showed that CD133 expression was an independent prognostic factor of patients with OS. To test for direct participation of CD133, we separated CD133+ and CD133− cells in the MG63 cell line using magnetic-activated cell sorting and found that CD133+ cells were more active in migration by scratch wound-healing assay and invasion by Matrigel invasion assay compared with CD133− cells. Elevated mRNA expression of the stemness gene octamer-binding transcription factor 4 (Oct-4) and NANOG, and the metastasis-related receptor C-X-C chemokine receptor type 4 (CXCR4) were also found in CD133+ cells by reverse transcription-polymerase chain reaction. Thus, expression of CD133 was correlated with lung metastasis and poor prognosis in OS patients. CD133+ cells may be a type of cancer stem cell with high expression of self-renewal capacity and metastasis-related genes.
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