Expression analysis of genes associated with human osteosarcoma tumors shows correlation of RUNX2 overexpression with poor response to chemotherapy.
BACKGROUND
Human osteosarcoma is the most common pediatric bone tumor. There is limited understanding of the molecular mechanisms underlying osteosarcoma oncogenesis, and a lack of good diagnostic as well as prognostic clinical markers for this disease. Recent discoveries have highlighted a potential role of a number of genes including: RECQL4, DOCK5, SPP1, RUNX2, RB1, CDKN1A, P53, IBSP, LSAMP, MYC, TNFRSF1B, BMP2, HISTH2BE, FOS, CCNB1, and CDC5L.


METHODS
Our objective was to assess relative expression levels of these 16 genes as potential biomarkers of osteosarcoma oncogenesis and chemotherapy response in human tumors. We performed quantitative expression analysis in a panel of 22 human osteosarcoma tumors with differential response to chemotherapy, and 5 normal human osteoblasts.


RESULTS
RECQL4, SPP1, RUNX2, and IBSP were significantly overexpressed, and DOCK5, CDKN1A, RB1, P53, and LSAMP showed significant loss of expression relative to normal osteoblasts. In addition to being overexpressed in osteosarcoma tumor samples relative to normal osteoblasts, RUNX2 was the only gene of the 16 to show significant overexpression in tumors that had a poor response to chemotherapy relative to good responders.


CONCLUSIONS
These data underscore the loss of tumor suppressive pathways and activation of specific oncogenic mechanisms associated with osteosarcoma oncogenesis, while drawing attention to the role of RUNX2 expression as a potential biomarker of chemotherapy failure in osteosarcoma.
Sadikovic
Bekim
B
Department of Pathology and Molecular Medicine, Richardson Labs, Queen's University, Kingston, K7L 3N6 Canada.
Thorner
Paul
P
Chilton-Macneill
Susan
S
Martin
Jeff W
JW
Cervigne
Nilva K
NK
Squire
Jeremy
J
Zielenska
Maria
M
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D012516:Osteosarcoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D012189:Retrospective Studies; D017211:Treatment Failure; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D050659:Core Binding Factor Alpha 1 Subunit; D012333:RNA, Messenger; C493709:RUNX2 protein, human
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