Osteosarcoma is characterised by reduced expression of markers of osteoclastogenesis and antigen presentation compared with normal bone.
Osteosarcoma is characterised by reduced expression of markers of osteoclastogenesis and antigen presentation compared with normal bone.
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DOI：
10.1038/sj.bjc.6605723
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发表时间：
2010-06-29
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
骨肉瘤（OS）是儿童和青少年中最常见的原发性骨肿瘤。对化疗反应不良的患者有更高的转移性疾病风险，5年生存率仅为10-20%。因此，确定针对骨肉瘤的特异性分子靶点，或者更具体地说，转移性骨肉瘤，将是开发新的治疗策略以改善患者预后的关键。我们对化疗初治OS活检和非恶性骨活检进行了转录组学分析，以鉴定OS特异性的差异表达基因，这可以为OS生物学和化疗耐药提供见解。对OS转录组的统计分析发现了几个金属硫蛋白家族成员的差异表达，以及参与抗原呈递的基因的解除管制。肿瘤也表现出ID1的显著表达增加和S100A8的深度下调，突出了它们作为OS治疗靶点的潜力。最后，我们发现骨肉瘤与破骨细胞生成和抗原呈递活性受损之间存在显著相关性。在化疗耐药的OS样本中，破骨细胞生成和抗原呈递活性的降低更为明显。我们的研究结果表明，OS显示的基因特征与抗原呈递活性降低、化疗耐药性增强和破骨细胞生成受损一致。此外，这些改变在化疗耐药的OS肿瘤样本中更为明显。
Osteosarcoma (OS) is the most common primary bone tumour in children and adolescents. Patients who respond poorly to chemotherapy have a higher risk of metastatic disease and 5-year survival rates of only 10–20%. Therefore, identifying molecular targets that are specific for OS, or more specifically, metastatic OS, will be critical to the development of new treatment strategies to improve patient outcomes. We performed a transcriptomic analysis of chemo-naive OS biopsies and non-malignant bone biopsies to identify differentially expressed genes specific to OS, which could provide insight into OS biology and chemoresistance. Statistical analysis of the OS transcriptomes found differential expression of several metallothionein family members, as well as deregulation of genes involved in antigen presentation. Tumours also exhibited significantly increased expression of ID1 and profound down-regulation of S100A8, highlighting their potential as therapeutic targets for OS. Finally, we found a significant correlation between OS and impaired osteoclastogenesis and antigen-presenting activity. The reduced osteoclastogenesis and antigen-presenting activity were more profound in the chemoresistant OS samples. Our results indicate that OS displays gene signatures consistent with decreased antigen-presenting activity, enhanced chemoresistance, and impaired osteoclastogenesis. Moreover, these alterations are more pronounced in chemoresistant OS tumour samples.
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影响因子：
8.7
作者：
Lanier LL
通讯作者：
Lanier LL
DOI：
10.1083/jcb.148.4.665
发表时间：
2000-02-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chellaiah M;Kizer N;Silva M;Alvarez U;Kwiatkowski D;Hruska KA
通讯作者：
Hruska KA
人类嗜中性粒细胞衍生的组织蛋白酶G和Azurocidin/cap37鉴定为单核细胞和中性粒细胞的趋化剂。
DOI：
10.1084/jem.186.5.739
发表时间：
1997-08-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chertov O;Ueda H;Xu LL;Tani K;Murphy WJ;Wang JM;Howard OM;Sayers TJ;Oppenheim JJ
通讯作者：
Oppenheim JJ
影响因子：
15.9
作者：
Kansara, Maya;Tsang, Michael;Thomas, David M.
通讯作者：
Thomas, David M.
影响因子：
5.8
作者：
Goldstein, Oliver G.;Hajiaghamohseni, Laela M.;Haque, Azizul
通讯作者：
Haque, Azizul