Reduced expression of BIRC2 and BIRC3 associated with longer survival in pediatric high-grade gliomas

Inhibitors of apoptosis proteins (IAPs), coded by BIRC genes, are cellular checkpoints that can regulate and inhibit pro-apoptotic caspase signaling. Overexpression of BIRC genes has been associated with cancer progression, multidrug resistance, poor prognosis, and shorter survival in several types of cancer. Using quantitative real-time polymerase chain reaction, we examined the expression of IAP family genes and their regulators: NAIP, BIRC2, BIRC3, XIAP, BIRC5, BIRC6, BIRC7, CASP3, CASP9, DIABLO and XAF1. We also evaluated the impact of clinical parameters (programmed death receptor 1 [PD1] expression, oligodendrocyte transcription factor 2 [Olig2] expression, Ki-67 antigen expression, tumor protein p53 expression in tumor cells, patient survival time, and progression-free survival) on gene expression levels. The expression of BIRC3 (p = 0.049), NAIP (p = 0.008), and XAF1 (p = 0.032) was significantly higher in tumors negative for Ki67, whereas the remaining genes showed no significant correlation with Ki67 expression. In contrast, BIRC2 (r=-0.478 p < 0.05) and BIRC3 (r=-0.536 p < 0.05) expression levels were negatively correlated with overall survival. A similar negative association was observed between progression-free survival and the expression of BIRC2 (r=–0.481, p < 0.05) and BIRC3 (r=-0.540, p < 0.05). To our knowledge, this is the first study to comprehensively assess the relationship between the expression of IAP family genes and their regulators in a homogeneous group of patients diagnosed with pediatric high-grade gliomas (pHGGs). Our findings provide new insights into molecular mechanisms involved in the pathogenesis of pHGGs, however, these preliminary results require confirmation in larger and more detailed studies.