Uckun Fatih M, Qazi Sanjive, Trieu Vuong
Ares Pharmaceuticals, Immuno-Oncology Program, St. Paul, MN 55110, USA.
Oncotelic Therapeutics, 29397 Agoura Road, Suite 107, Agoura Hills, CA 91301, USA.
Cancers (Basel). 2023 Mar 9;15(6):1676. doi: 10.3390/cancers15061676.
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.
在此，我们报告称，新诊断的儿童弥漫性脑桥内在型胶质瘤（DIPG）患者的肿瘤样本中，转化生长因子β2（TGFB2）信使核糖核酸（mRNA）水平显著高于对照脑桥样本，这与上调TGFB2基因表达的转录因子表达增加相关。我们的研究还表明，基于RNA测序（RNAseq）的高TGFB2 mRNA水平是DIPG患者预后不良的一个指标，但对于儿童胶质母细胞瘤（GBM）患者或肿瘤位于脑桥/脑干以外的儿童弥漫性中线胶质瘤（DMG）患者则不然。值得注意的是，肿瘤样本中TGFB2 mRNA表达水平高的DIPG患者的总生存期（OS）和无进展生存期（PFS）明显更差。相比之下，肿瘤样本中转化生长因子β3（TGFB3）mRNA表达水平高与DIPG患者明显更好的生存结果相关，而转化生长因子β1（TGFB1）表达水平高则无预后意义。我们的研究填补了我们对儿童高级别胶质瘤中高TGFB2表达的临床意义理解上的重大空白。
