Osteosarcoma (OS) accounts for 56% of malignant bone cancers and 6% of all cancer cases in children and adolescents1. Pulmonary metastasis occurs in approximately 50% of patients with a 5 year survival rate of only 20%, while non-metastatic OS has an expected 5 year survival rate of 70%. In order to improve survival in the metastatic cohort of patients it is crucial to identify genes and pathways that drive the metastatic behaviour of OS for the identification of therapeutic targets.
To identify markers that may define inherent metastatic OS we conducted microarray-based comparative profiling analysis of clonal variants from an inherently metastatic cell line, KHOS. Two highly metastatic (C1 and C6) and two poorly metastatic clones (C4 and C5) were compared in the transcriptomic screen.
Vascular endothelial growth factor A (VEGFA) and two other novel genes were identified as potential markers for OS metastasis with 2-4 fold increased expression in highly metastatic clonal variants when compared to poorly metastatic clonal variants. The transcriptomic expression of VEGFA and the two new markers was also investigated in non-malignant bone (NB), OS patients with non-metastatic (NM) and metastatic (M) disease. All three markers were found to be highly expressed in 29-42% of M-OS with little to no expression seen in NB and NM-OS. VEGFA has also been shown to be a promising target in the treatment of OS development and metastasis2. This further supports the identification of the two novel OS metastasis markers.
VEGFA and two novel markers were found to be up-regulated in highly metastatic KHOS clonal variants and their identification was further supported by expression levels in metastatic OS patient biopsies. These markers are promising targets which will require further validation as possible drivers of OS metastasis and therapeutic targets.