Tenascin-C as a prognostic biomarker in osteosarcoma?

Background Treating metastatic osteosarcoma has been challenged in past decades. Extracelluar matrix (ECM)proteins play an important role in the progression of osteosarcoma as they are pivotal components of the tumormicroenvironment. Here, we identified potential genes belonging to the ECM and characterized the roles of these genesin the progression of osteosarcoma and their association with outcomes.Methods Osteosarcoma parental cell line MG63 and its derivative MG63-A1 with a high metastatic potential underwentoligonucleotide microarray analysis. Gene ontology analysis was used to screen deregulated genes between the 2 celllines which were either upregulated or downregulated by more than 4 fold, particularly focusing on mRNAs encodingextracellular matrix proteins. The expression of resulting candidate genes was then validated by reverse transcriptionPCRfor mRNA expression as well as Western blotting for protein expression. Immunohistochemistry was performed on37 osteosarcoma specimens to examine the potential role of the candidate genes in a clinical context.Results Microarray data and gene ontology analysis showed that Tenascin-C, a critical component of the ECM, issignificantly down-regulated in the highly metastatic cell line MG63-A1 compared with the parental osteosarcoma cell lineMG63-wt. This finding was validated at mRNA and protein levels. Immunohistochemical analysis found that Tenascin-C islocated in the intercellular space in osteosarcoma specimens. Furthermore, low-grade Tenascin-C expression (less than20%) in osteosarcoma specimens was associated with poor survival.Conclusions Tenascin-C expression level correlates with the survival of osteosarcoma patients. Its biologicalfunctional role and underlying molecular mechanisms in the progression of osteosarcoma needs further investigation.