Osteosarcoma is characterised by reduced expression of markers of osteoclastogenesis and antigen presentation compared with normal bone.
BACKGROUND
Osteosarcoma (OS) is the most common primary bone tumour in children and adolescents. Patients who respond poorly to chemotherapy have a higher risk of metastatic disease and 5-year survival rates of only 10-20%. Therefore, identifying molecular targets that are specific for OS, or more specifically, metastatic OS, will be critical to the development of new treatment strategies to improve patient outcomes.


METHODS
We performed a transcriptomic analysis of chemo-naive OS biopsies and non-malignant bone biopsies to identify differentially expressed genes specific to OS, which could provide insight into OS biology and chemoresistance.


RESULTS
Statistical analysis of the OS transcriptomes found differential expression of several metallothionein family members, as well as deregulation of genes involved in antigen presentation. Tumours also exhibited significantly increased expression of ID1 and profound down-regulation of S100A8, highlighting their potential as therapeutic targets for OS. Finally, we found a significant correlation between OS and impaired osteoclastogenesis and antigen-presenting activity. The reduced osteoclastogenesis and antigen-presenting activity were more profound in the chemoresistant OS samples.


CONCLUSIONS
Our results indicate that OS displays gene signatures consistent with decreased antigen-presenting activity, enhanced chemoresistance, and impaired osteoclastogenesis. Moreover, these alterations are more pronounced in chemoresistant OS tumour samples.
Endo-Munoz
L
L
The University of Queensland, Diamantina Institute for Cancer, Immunology and Metabolic Medicine, Level 4, R Wing, Princess Alexandra Hospital, Queensland 4102, Australia.
Cumming
A
A
Sommerville
S
S
Dickinson
I
I
Saunders
N A
NA
D000293:Adolescent; D000328:Adult; D000368:Aged; D017951:Antigen Presentation; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D040501:Calgranulin A / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics; D008297:Male; D010010:Osteoclasts / Q000502:physiology*; D010012:Osteogenesis; D012516:Osteosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology
D040501:Calgranulin A; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1