High Intra-Tumor Transforming Growth Factor Beta 2 Level as a Predictor of Poor Treatment Outcomes in Pediatric Diffuse Intrinsic Pontine Glioma

Abstract

Here, we report that tumor samples from newly diagnosed pediatric diffuse intrinsic pontine glioma (DIPG) patients express significantly higher levels of transforming growth factor beta 2 (TGFB2) messenger ribonucleic acid (mRNA) than control pons samples, which correlated with augmented expression of transcription factors that upregulate TGFB2 gene expression. Our study also demonstrated that RNA sequencing (RNAseq)-based high TGFB2 mRNA level is an indicator of poor prognosis for DIPG patients, but not for pediatric glioblastoma (GBM) patients or pediatric diffuse midline glioma (DMG) patients with tumor locations outside of the pons/brainstem. Notably, DIPG patients with high levels of TGFB2 mRNA expression in their tumor samples had significantly worse overall survival (OS) and progression-free survival (PFS). By comparison, high levels of transforming growth factor beta 3 (TGFB3) mRNA expression in tumor samples was associated with significantly better survival outcomes of DIPG patients, whereas high levels of transforming growth factor beta 1 (TGFB1) expression was not prognostic. Our study fills a significant gap in our understanding of the clinical significance of high TGFB2 expression in pediatric high-grade gliomas.