E for aberrant Wnt signaling in the pathobiology and progression of OS. The Wnt pathway may represent a promising source of novel therapeutic targets and disease progression biomarkers. Another common pathway relevant in metastasis is the "Cell adhesion/chemokines and adhesion", which was identified at both the genomic and proteomic levels.Flores et al. BMC Systems Biology 2012, 6:50 http://www.biomedcentral.com/1752-0509/6/Page 12 ofChemokine ligands and their cognate receptors have been extensively implicated in the progression and metastasis of multiple tumors such as melanoma, breast cancer, prostate cancer, and others [49-53]. In OS, research has revealed a complex interaction between chemokine ligand/receptor axis, and their role in tumor invasion, metastasis and patient prognosis [54]. Our group previously reported that expression of two CXC chemokines were elevated in tumor and plasma of pediatric OS patients, and their levels correlated with patient outcomes [55]. Several of the CXC chemokines were also identified by the topological analysis in this study, including CXCL12 which has been directly associated to metastasis in OS and other tumors [56]. Identification of the significant topological nodes within such complex networks could help identify the key players and delineate their roles in cell adhesion, invasion and other important metastasis functions. In addition to the identification of therapeutic 3-Bromo-4-(propan-2-yloxy)aniline hydrochloride targets, identification of tumor-derived biomarkers for early detection of disease progression and metastasis is a critical component for personalized medicine. As previously noted, characterization of key hidden nodes could facilitate the identification of candidate biomarkers for metastatic OS. Because of the diversity of the human PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/10485401 proteome and limitations of the current proteomic methods, targeting specific subproteomes that are likely to be secreted into the blood stream, such as the glycoproteome, will improve the likelihood of identifying tumor-derived circulating biomarkers. In this study, we characterized the N-linked glycoproteome due to their involvement in metastatic OS as evidenced by the glycogene PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26843381 analysis, and their frequent localization in the cellular membrane and extracellular space. In spite of the limited number of glycoproteins identified in this study, the topological analysis revealed common significant pathways between the differentially regulated glycoproteins and genes in both OS models. Using this analysis, we can prioritize the up-regulated glycoproteins and upregulated genes as well as the hidden molecules that may serve as biomarkers for the disease or metastasis in the future validation, such as proteins in 5,6-Dichloro-1H-indole the TGF beta (i.e. TGFB1, TGFBR1, TGFBR2) and MAP kinase (MAPK1, MAPK3, MAP3K1,MAP3K8) families identified by topological analysis. Despite the encouraging results, we recognize that there are limitations in the current study. For instance, the cell line models used in our study represents a significant limitation. Although the in vitro models provide a convenient and renewable platform that cannot be surpassed by clinical specimens, it may not faithfully reflect the behavior of tumor cells in vivo. Therefore, future directions include the development of orthotopic xenograft mouse models to recapitulate and validate theresults obtained in this study. In addition, the characterized N-linked glycoproteins with an affinity for the WGA lectin represent a restricted number of proteins, which is typi.