Key result
AURKA and AURKB overexpression is linked to lower event-free survival in pediatric adrenocortical tumors.
Why the study?
Pediatric adrenocortical tumors are rare malignancies with limited treatment impact on survival in advanced disease, necessitating discovery of potential target genes for new therapies.
Observational (n=60)
p-value: p=0.002 for AURKA, 0.03 for AURKB (multivariate)
Overexpression of AURKA and AURKB in pediatric adrenocortical tumors is associated with worse event-free survival, suggesting they may be prognostic markers and potential therapeutic targets.
BACKGROUND: Pediatric adrenocortical tumors (ACT) are rare malignancies and treatment has a small impact on survival in advanced disease and the discovery of potential target genes could be important in new therapeutic approaches. METHODS: The mRNA expression levels of spindle checkpoint genes AURKA, AURKB, BUB, and BUBR1 were analyzed in 60 children with ACT by quantitative real time PCR. The anticancer effect of ZM447439, an experimental AURK inhibitor, was analyzed in a primary childhood ACT culture carrying the TP53 p.R337H mutation. RESULTS: A significant association was observed between malignancy as defined by Weiss score ≥3 and higher AURKA (2.0-fold, P = 0.01), AURKB (7.0-fold, P = 0.007), and BUBR1 (5.8-fold, P = 0.007) gene expression, and between unfavorable event (death or relapse) and higher expression of AURKA (6.0-fold, P = 0.034) and AURKB (17-fold, P = 0.013). Overexpression of AURKA and AURKB was associated with lower event-free survival in uni- (P < 0.001 and P = 0.006, respectively) and multivariate (P = 0.002 and P = 0.03, respectively) analysis. Significant lower Event free survival (EFS) was also observed in patients with moderate/strong immunostaining to AURKA (P = 0.012) and AURKB (P = 0.045). ZM447439 was able to induce inhibition of proliferation and colony formation in a primary childhood ACT culture carrying the TP53 p.R337H mutation. CONCLUSION: Our results suggest that AURKA and AURKB overexpression in pediatric ACT may be related to more aggressive disease and the inhibition of these proteins could be an interesting approach for the treatment of these tumors.
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Borges et al. (2013) conducted an observational in childhood adrenocortical tumors (ACT) (n=60). AURKA and AURKB overexpression vs. lower expression was evaluated on event-free survival (p=0.002 for AURKA, 0.03 for AURKB (multivariate)). Overexpression of AURKA and AURKB in pediatric adrenocortical tumors was significantly associated with lower event-free survival in multivariate analysis (P=0.002 and P=0.03, respectively).
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