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

Abstract

Abstract 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.