In silico Molecular Target Validation Demonstrates Transforming Growth Factor Beta 2 is Strongly Expressed in Pediatric Diffuse Intrinsic Pontine Glioma and Glioblastoma Multiforme
Fatih M. Uckun, Vuong Trieu, Larn Hwang, Sanjive Qazi
Citation : Uckun FM, Trieu V,Hwang L, Qazi S. In silico Molecular Target Validation Demonstrates Transforming Growth Factor Beta 2 is Strongly Expressed in Pediatric Diffuse Intrinsic Pontine Glioma and Glioblastoma Multiforme. Clin Res Pediatr 2019;2(1):1-10.
Aim: The purpose of the present study was to perform a comprehensive analysis of transforming growth factorbeta 2 (TGFβ2) gene expression in pediatric diffuse intrinsic pontine glioma (DIPG) and glioblastoma multiforme (GBM).
Materials and Methods: We performed a meta-analysis of TGFβ2 gene expression for primary tumor specimens
from 29 pediatric DIPG and 82 pediatric GBM (p-GBM) patients in the publicly available archived datasets GSE26576,
GSE19578, GSE32374, GSE34824, and GSE49822.
Results: Our data provide unprecedented evidence that TGFβ2 is expressed at high levels in pediatric DIPG as well as p-GBM. Three TGFβ2 probe sets exhibited increased levels of expression in DIPG patients (n = 29): Mean fold difference for Probeset 228121_at was 2.48 (linear contrast P = 3.40 X 10-4); Probeset 220407_s_at was 2.00 (linear contrast P = 0.006); and Probeset 209909_s_at was 1.81 (linear contrast P = 0.0185). One of the TGFβ2 probe sets was also exhibited the highest level of mean expression in DIPG patients; TGFB2_228121_at (mean = 9.25 ± 0.18 log2 robust multiarray analysis [RMA]) and YAP1_224894_at (mean = 8.55 ± 0.19 log2 RMA). Similar results were obtained for p-GBM patients (n = 82). Three probe sets for TGFβ2 significantly upregulated >2-fold in p-GBM patients (Probesets: 209909_s_at [fold change = 4.03, P = 1.78 X 10-5]; 228121_at [fold change = 3.57, P = 8.81 X 10-5]; and 220407_s_at [fold change = 2.73, P = 0.0019]). The three probe sets with highest expression levels in p-GBM were TGFB2_228121_at (mean = 9.24 ± 0.15), TGFB3_209747_at (mean = 6.99 ± 0.086), and TGFB1_203085_s_at (mean = 6.80 ± 0.16).
Conclusions: Our findings indicate that TGFβ2 gene product may serve as a target for immunotherapy in pediatric DIPG and GBM. Our findings also significantly expand the current knowledge of TGFβ2 expression in brain tumors and provide new evidence that TGFβ2 gene and its interactome are expressed in pediatric DIPG and GBM at significantly higher levels than in normal tissues or low-grade gliomas. This previously unknown differential expression profile uniquely indicates that TGFβ2 would be an attractive molecular target for the treatment of pediatric DIPG and GBM.
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