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

## TL;DR

Lower levels of BIRC2 and BIRC3 genes are linked to longer survival in children with aggressive brain tumors called high-grade gliomas.

## Contribution

This is the first study to comprehensively analyze IAP gene expression in pediatric high-grade gliomas and link BIRC2/BIRC3 levels to survival outcomes.

## Key findings

- BIRC2 and BIRC3 expression levels were negatively correlated with overall and progression-free survival in pediatric high-grade glioma patients.
- Higher expression of BIRC3, NAIP, and XAF1 was observed in Ki67-negative tumors.
- The study provides new insights into molecular mechanisms underlying pediatric high-grade glioma pathogenesis.

## 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.

The online version contains supplementary material available at 10.1038/s41598-026-35887-7.