a systems biology approach reveals common metastatic pathways in osteosarcoma系统生物学的方法揭示了骨肉瘤中常见的转移途径.pdfVIP

Flores et al. BMC Systems Biology 2012, 6:50 /1752-0509/6/50 RESEARCH ARTICLE Open Access A systems biology approach reveals common metastatic pathways in osteosarcoma 1,2 1,2 1,2 1,2 1,2 4 5 Ricardo J Flores , Yiting Li , Alexander Yu , Jianhe Shen , Pulivarthi H Rao , Serrine S Lau , Marina Vannucci , Ching C Lau1,2,3 and Tsz-Kwong Man1,2,3* Abstract Background: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. The survival rate of patients with metastatic disease remains very dismal. Nevertheless, metastasis is a complex process and a single-level analysis is not likely to identify its key biological determinants. In this study, we used a systems biology approach to identify common metastatic pathways that are jointly supported by both mRNA and protein expression data in two distinct human metastatic OS models. Results: mRNA expression microarray and N-linked glycoproteomic analyses were performed on two commonly used isogenic pairs of human metastatic OS cell lines, namely HOS/143B and SaOS-2/LM7. Pathway analysis of the differentially regulated genes and glycoproteins separately revealed pathways associated to metastasis including cell cycle regulation, immune response, and epithelial-to-mesenchymal-transition. However, no common significant pathway was found at both genomic and proteomic levels between the two metastatic models, suggesting a very different biological nature of the cell lines. To address this issue, we used a topological significance analysis based on a “shortest-path” algorithm to identify topological nodes, which uncovered additional biological information with respect to the genomic and glycoproteomic pr