Proteomic analysis of osteogenic sarcoma: association of tumour necrosis factor with poor prognosis.

Cates JM, Friedman DB, Seeley EH, Dupont WD, Schwartz HS, Holt GE, Caprioli RM, Young PP
Int J Exp Pathol. 2010 91 (4): 335-49

PMID: 20353421 · PMCID: PMC2962892 · DOI:10.1111/j.1365-2613.2010.00711.x

A significant proportion of patients with osteogenic sarcoma die from lung metastasis within 5 years of diagnosis. Molecular signatures that predict pulmonary metastasis from primary osteogenic sarcoma and identify those patients at risk would be clinically useful as prognostic markers. Protein expression profiles of two clonally related murine osteogenic sarcoma cell lines with low (K12) and high (K7M2) metastatic potential were compared using two different proteomic technologies, two-dimensional difference gel electrophoresis and cell profiling by matrix-assisted laser desorption/ionization mass spectrometry. Interrogation of a molecular pathways network database suggested several additional candidate molecules that potentially predict metastatic potential of primary osteogenic sarcoma. Two such proteins, macrophage migration inhibitory factor and tumour necrosis factor were selected for further validation studies. Western blots confirmed increased expression of both cytokines in K7M2 cells compared to K12 cells. Levels of migration inhibitory factor and tumour necrosis factor were semi-quantitatively measured in human osteogenic sarcoma samples by immunohistochemistry and were correlated with clinicopathologic parameters and patient outcomes. Multivariate survival analysis demonstrated that tumour necrosis factor expression in chemotherapy naïve osteogenic sarcoma is an independent prognostic factor for overall and metastasis-free survival. No significant differences in adverse outcomes were observed based on macrophage migration inhibitory factor expression.

MeSH Terms (33)

Adolescent Adult Aged Aged, 80 and over Animals Biomarkers, Tumor Blotting, Western Bone Neoplasms Cell Line, Tumor Child Child, Preschool Electrophoresis, Gel, Two-Dimensional Female Humans Immunohistochemistry Intramolecular Oxidoreductases Kaplan-Meier Estimate Macrophage Migration-Inhibitory Factors Male Mice Middle Aged Neoplasm Staging Osteosarcoma Proportional Hazards Models Proteomics Risk Assessment Risk Factors Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Time Factors Tissue Array Analysis Treatment Outcome Tumor Necrosis Factor-alpha Young Adult

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