Research Paper Volume 14, Issue 9 pp 3856—3873
The immune regulation of BCL3 in glioblastoma with mutated IDH1
- 1 Department of Neurosurgery, Chongqing Medical University, Chongqing, China
- 2 Chongqing University Three Gorges Hospital, Wanzhou, Chongqing, China
- 3 Chongqing University, Shapingba, Chongqing, China
Received: September 29, 2021 Accepted: January 25, 2022 Published: April 29, 2022https://doi.org/10.18632/aging.204048
How to Cite
Copyright: © 2022 Fan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: Glioblastoma in the brain is the most malignant solid tumor with a poor prognosis. Screening critical targets and exploring underlying mechanisms will be a benefit for diagnoses and treatment. IDH1 mutation (R132) was used to distinguish glioblastoma grade and predict prognosis as a significant marker. However, the manner of IDH1 mutation regulating glioblastoma development was still unclear.
Methods: To study the function of IDH1 mutation, multi-type sequencing data (transcriptome, methylation and copy number variation) from the GEO and TCGA database were analyzed using bioinformatics techniques. The biological functions of IDH1 mutation (R132) would be comprehensively evaluated from the regulatory networks, tumor immune microenvironment and clinical relevance. Then the analysis result would be validated by experimental techniques.
Results: Compared with adjacent tissues, IDH1 was up-regulated in glioblastoma, which also positively correlated with the malignant degree and a poor prognosis. To further study the mechanism of mutated IDH1 (R132) function, 5 correlated genes (FABP5, C1RL, MIR155HG, CSTA and BCL3) were identified by different expression gene screening, enrichment analysis and network construction successively. Among them, the BCL3 was a transcription factor that may induce IDH1expression. Through calculating the correlation coefficient, it was found that in IDH1mut glioblastoma, the dendritic cell infiltration was reduced which may result in a better prognosis. In addition, the level of IDH1, FABP5, C1RL, MIR155HG, CSTA and BCL3 might also influence lymphocytes infiltration (eg. CD4+ T cell) and chemokine expression (CXCL family).
Conclusions: IDH1 may participate in pathological mechanisms of glioblastoma via expression alteration or gene mutation. Furthermore, IDH1 mutation might improve prognosis via suppressing the expression of FABP5, C1RL, MIR155HG, CSTA and BCL3. Meanwhile, it was identified that BCL3 might perform similar immunomodulatory functions with IDH1 as an upstream transcript factor.
GBM: glioblastoma; CNS: central nervous system; IDH1: isocitrate dehydrogenase 1; α-KG: α-ketoglutarate; NADPH: nicotinamide adenine dinucleotide phosphate; G-CIMP: glioma-CpG island methylator phenotype; BCL-3: B-cell CLL/lymphoma 3; OS: overall survival; BP: biological process; CC: cellular component; temozolomide: molecular function; HR: hazard ratio; FDR: false discovery rate; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; IHC: Immunohistochemistry; HSD: honest significant difference; TSS: transcription start site.