Research Paper Volume 12, Issue 8 pp 7112—7128

Identification of immunologic subtype and prognosis of GBM based on TNFSF14 and immune checkpoint gene expression profiling

Shengrong Long 1, *, , Mingdong Li 1, *, , Jia Liu 1, , Yi Yang 1, , Guangyu Li 1, ,

  • 1 Department of Neurosurgery, First Affiliated Hospital of China Medical University, Shenyang, China
* Equal contribution

received: October 24, 2019 ; accepted: March 24, 2020 ; published: April 20, 2020 ;

https://doi.org/10.18632/aging.103065
How to Cite

Copyright © 2020 Long 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.

Abstract

Immune-checkpoint therapy has failed to show significant benefit in glioblastoma (GBM) patients. Immunologic subtypes of GBM are necessary to identify patients who might benefit from immune-checkpoint therapy. This study reviewed 152 GBM samples from The Cancer Genome Atlas (TCGA) and 214 GBM samples from Chinese Glioma Genome Atlas (CGGA). Correlation analysis showed that immune checkpoint genes (ICGs) were mainly positively correlated. The prognostic analysis of the overall survival showed that there was a significant correlation between the overall survival (OS) and the prognosis of ICGs, in which the TNFSF14 gene was a significant adverse prognostic factor. Combined with TMB and neoantigens, we found that TNFSF9 and CD27 were significantly negatively correlated with TMB and neoantigens. The association between adaptive immune pathway genes and ICG expression showed that they were positively correlated with ICGs, indicating that adaptive immune pathway genes have a certain regulatory effect on the expression of ICGs. The analysis of clinical features of the samples showed that the higher the expression of ICGs, the more likely to be correlated with mutant isocitrate dehydrogenase (IDH), while the lower the expression level of IDH, the more likely to be significantly correlated with the primary GBM. Survival analysis showed that low expression of PD-L1, IDO1, or CTLA4 with TNFSF14 in the low expression group had the best prognosis, while high expression of IDO1 or CD274 with TNFSF14 in the high expression group and low expression of CTLA4 with TNFSF14 in the high expression group had the worst prognosis. We conclude that TNFSF14 is a biomarker to identify immunologic subtype and prognosis with other ICGs in GBM and may serve as a potential therapeutic target.

Abbreviations

GBM: glioblastoma multiform; TCGA: the Cancer Genome Atlas; CGGA: Chinese Glioma Genome Atlas; WHO: World Health Organization; LGG: low-grade gliomas; HGG: high-grade gliomas; TMZ: temozolomide; OS: overall survival; CAR-T: chimeric antigen receptor T-cell; DC: dendritic cell; CTLA-4: cytotoxic T-lymphocyte-associated protein 4; PD-1: programmed cell death protein 1; NSCLC: non-small cell lung cancer; TAM: tumor-associated macrophage; NK: natural killer; ICG: immune checkpoint genes; MMRd: mismatch repair defect; TMB: tumor mutation burden; FPKM: fragments per kilobase million; KM: Kaplan–Meier; TNF: tumor necrosis factor; LT β-R: lymphotoxin β-receptor; DcR3: decoy receptor 3; HVEM: herpesvirus entry medium.