He Aina, Qi Weixiang, Huang Yujing, Feng Tao, Chen Jie, Sun Yuanjue, Shen Zan, Yao Yang
Departments of Oncology and.
Exp Ther Med. 2012 Sep;4(3):435-441. doi: 10.3892/etm.2012.603. Epub 2012 Jun 8.
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.
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。已发现CD133是某些肿瘤类型的预后因素。然而，CD133表达与OS预后之间的关联仍不清楚。在本研究中，我们分析了OS中CD133表达与临床因素及总生存期的关联，并进一步研究了其在体外转移中的潜在作用。我们通过免疫组织化学在65.7%（46/70）的OS样本中发现了CD133表达，通过卡方检验分析其与肺转移呈正相关（P = 0.002），并且使用对数秩检验通过Kaplan-Meier方法比较发现其与较短的总生存时间相关（P = 0.000）。多因素分析表明，CD133表达是OS患者的独立预后因素。为了测试CD133的直接参与情况，我们使用磁珠分选法在MG63细胞系中分离出CD133(+)和CD133(-)细胞，发现与CD133(-)细胞相比，CD133(+)细胞在划痕伤口愈合试验中的迁移能力以及在基质胶侵袭试验中的侵袭能力更强。通过逆转录-聚合酶链反应还发现CD133(+)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（CXCR4）的mRNA表达升高。因此，CD133的表达与OS患者的肺转移和不良预后相关。CD133(+)细胞可能是一种具有高自我更新能力和转移相关基因表达的癌症干细胞。
