An analysis of gene expression profile of osteosarcoma cells in the bone and peripheral blood with DNA microarray. -Identification of marker genes for osteosarcoma using hierarchical clustering algorithm. -

基于DNA微阵列技术分析骨组织中5147个基因的mRNA表达。通过系统聚类和散点图分析鉴定差异表达基因。逆转录聚合酶链式反应证实四种基因[2型胶原(COL2)、细胞外超氧化物歧化酶(SOD)、纤溶酶原激活物(u-PA)和DDR1]的mRNA表达差异。此外，免疫组织化学显示，u-PA在软骨与骨交界处的软骨细胞和软骨破骨细胞中呈阳性，提示其在软骨的吸收和重塑中起重要作用。DDR1在骨肉瘤细胞中受辐射上调，并受最重要的抑癌基因之一P53的调控。已知的功能强烈提示DDR1基因在骨肉瘤的肿瘤发生中起重要作用。我们还发现CDK4和MDM2基因在高分化脂肪肉瘤中过表达，这两个基因是细胞周期相关基因，受P53基因调控。这些基因是区分脂肪瘤和分化良好的脂肪肉瘤的潜在标记物。

DNA microarray-based analysis of mRNA expression of 5147 genes in bone tissue was performed. Differentially expressed genes were identified by hierarchical clustering and scatter plot analyses. Differential mRNA expression of four genes [collagen type 2 (COL2), extracellular superoxide dismutase (SOD), plasminogen activator (u-PA) and DDR1] were confirmed by reverse transcription polymerase chain reaction. Further, immunohistologically, u-PA was positive for chondrocytes and chondroclasts in the junction between cartilage and bone, implying its importance in resorption and remodeling of cartilaginous cartilage. DDR1 is upregulated by irradiation in osteosarcoma cells and is regulated by p53, which is one of most important tumor suppressor genes. Known function strongly suggest important roles for DDR1 genes in the tumorigenesis of osteosarcoma. We also identified cdk4 and mdm2 genes, which are cell cycle related genes and are regulated by p53 gene, are overexpressed in well-differentiated liposarcoma. These genes are potential marker for distinguish lipoma and well-differentiated liposarcoma.