Expression analysis of genes associated with human osteosarcoma tumors shows correlation of RUNX2 overexpression with poor response to chemotherapy
Expression analysis of genes associated with human osteosarcoma tumors shows correlation of RUNX2 overexpression with poor response to chemotherapy
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DOI：
10.1186/1471-2407-10-202
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发表时间：
2010-05-13
期刊：
影响因子：
3.8
通讯作者：
Zielenska, Maria
中科院分区：
文献类型：
--
作者：
Sadikovic, Bekim;Thorner, Paul;Zielenska, Maria
背景：人骨肉瘤是儿童最常见的骨肿瘤。目前对骨肉瘤发生的分子机制了解有限，缺乏良好的诊断和预后临床标志物。RECQL4、DOCK5、SPP1、RUNX2、RB1、CDKN1A、P53、IBSP、LSAMP、MYC、TNFRSF1B、BMP 2、HISTH2BE、FOS、CCNB1和CDC5L等基因在骨肉瘤发生和化疗反应中的相对表达水平。结果：RECQL 4、SPP 1、RUNX 2和IBSP在22例对化疗有不同反应的人骨肉瘤肿瘤和5例正常人成骨细胞中显著过表达，DOCK 5、CDKN 1A、RB 1、P53和LSAMP相对于正常成骨细胞的表达明显缺失。除了相对于正常成骨细胞在骨肉瘤肿瘤样品中过表达外，RUNX2是16个基因中唯一在对化疗反应较差的肿瘤中显示出显著过表达的基因。这些数据强调了肿瘤抑制途径的丧失和与骨肉瘤肿瘤发生相关的特定致癌机制的激活，同时引起人们对RUNX2表达作为骨肉瘤化疗失败的潜在生物标志物的关注。
Background: Human osteosarcoma is the most common pediatric bone tumor. There is limited understanding of the molecular mechanisms underlying osteosarcoma oncogenesis, and a lack of good diagnostic as well as prognostic clinical markers for this disease. Recent discoveries have highlighted a potential role of a number of genes including: RECQL4, DOCK5, SPP1, RUNX2, RB1, CDKN1A, P53, IBSP, LSAMP, MYC, TNFRSF1B, BMP2, HISTH2BE, FOS, CCNB1, and CDC5L.Methods: Our objective was to assess relative expression levels of these 16 genes as potential biomarkers of osteosarcoma oncogenesis and chemotherapy response in human tumors. We performed quantitative expression analysis in a panel of 22 human osteosarcoma tumors with differential response to chemotherapy, and 5 normal human osteoblasts.Results: RECQL4, SPP1, RUNX2, and IBSP were significantly overexpressed, and DOCK5, CDKN1A, RB1, P53, and LSAMP showed significant loss of expression relative to normal osteoblasts. In addition to being overexpressed in osteosarcoma tumor samples relative to normal osteoblasts, RUNX2 was the only gene of the 16 to show significant overexpression in tumors that had a poor response to chemotherapy relative to good responders.Conclusion: These data underscore the loss of tumor suppressive pathways and activation of specific oncogenic mechanisms associated with osteosarcoma oncogenesis, while drawing attention to the role of RUNX2 expression as a potential biomarker of chemotherapy failure in osteosarcoma.