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

Long, Shengrong; Li, Mingdong; Liu, Jia; Yang, Yi; Li, Guangyu

doi:10.18632/aging.103065

Cited by 18 publications

(22 citation statements)

References 45 publications

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“…Additionally, the authors observed more endothelial venules and T cell infiltration in solid tumors [ 35 ]. In a recent study, researchers determined that the expression of TNFSF14 negatively correlates with tumor mutation burden (TMB) in GBM and that TNFSF14 is a significant prognostic factor for poor OS [ 36 ]. TNFSF14 can promote the proliferation of Foxp3 + Tregs [ 37 ], and bind HVEM which are expressed on Foxp3 + Tregs to mediate the suppressive functions [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

A novel Foxp3-related immune prognostic signature for glioblastoma multiforme based on immunogenomic profiling

Guo

Zhang

Wang

et al. 2021

Aging

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Foxp3 + regulatory T cells (Treg) play an important part in the glioma immunosuppressive microenvironment. This study analyzed the effect of Foxsp3 on the immune microenvironment and constructed a Foxp3-related immune prognostic signature (IPS)for predicting prognosis in glioblastoma multiforme (GBM). Immunohistochemistry (IHC) staining for Foxp3 was performed in 72 high-grade glioma specimens. RNA-seq data from 152 GBM samples were obtained from The Cancer Genome Atlas database (TCGA) and divided into two groups, Foxp3 High (Foxp3_H) and Foxp3 Low (Foxp3_L), based on Foxp3 expression. We systematically analyzed the influence of Foxp3 on the immune microenvironment. Least Absolute Shrinkage and Selection Operator (LASSO) Cox analysis was conducted for immune-related genes that were differentially expressed between Foxp3_H and Foxp3_L GBM patients. We found a differential expression of Foxp3 in high-grade glioma tissues. The presence of Foxp3 was significantly associated with poor OS. From the four-gene IPS developed, GBM patients were stratified into low-risk and high-risk groups in both the training set and validation sets. Furthermore, we developed a novel nomogram to evaluate the overall survival in GBM patients. This study offers innovative insights into the GBM immune microenvironment and these findings contribute to individualized treatment and improvement in the prognosis for GBM patients.

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Section: Discussionmentioning

confidence: 99%

A novel Foxp3-related immune prognostic signature for glioblastoma multiforme based on immunogenomic profiling

Guo

Zhang

Wang

et al. 2021

Aging

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“…When we finished this manuscript, we found a study about LIGHT expression in GBM, which was presented by Long et al (2020). To further unravel the characterization and prognostic value of LIGHT in whole grades of glioma, we performed this analysis as a comprehensive study.…”

Section: Discussionmentioning

confidence: 99%

“…To date, the authors failed to find a comprehensive study about the characterization of LIGHT expression in pan-glioma. Only one article reported by Long et al (2020) described the role and prognostic value of LIGHT in GBM. In the present study, transcriptome data of 998 pan-glioma patients were analyzed to demonstrate the expression profile of LIGHT in pan-glioma molecularly and clinically.…”

Section: Introductionmentioning

confidence: 99%

Molecular and Clinical Characterization of LIGHT/TNFSF14 Expression at Transcriptional Level via 998 Samples With Brain Glioma

Yang¹,

et al. 2021

Front. Mol. Biosci.

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LIGHT, also termed TNFSF14, has been reported to play a vital role in different tumors. However, its role in glioma remains unknown. This study is aimed at unveiling the characterization of the transcriptional expression profiling of LIGHT in glioma. We selected 301 glioma patients with mRNA microarray data from the CGGA dataset and 697 glioma patients with RNAseq data from the TCGA dataset. Transcriptome data and clinical data of 998 samples were analyzed. Statistical analyses and figure generation were performed with R language. LIGHT expression showed a positive correlation with WHO grade of glioma. LIGHT was significantly increased in mesenchymal molecular subtype. Gene Ontology analysis demonstrated that LIGHT was profoundly involved in immune response. Moreover, LIGHT was found to be synergistic with various immune checkpoint members, especially HVEM, PD1/PD-L1 pathway, TIM3, and B7-H3. To get further understanding of LIGHT-related immune response, we put LIGHT together with seven immune signatures into GSVA and found that LIGHT was particularly correlated with HCK, LCK, and MHC-II in both datasets, suggesting a robust correlation between LIGHT and activities of macrophages, T-cells, and antigen-presenting cells (APCs). Finally, higher LIGHT indicated significantly shorter survival for glioma patients. Cox regression models revealed that LIGHT expression was an independent variable for predicting survival. In conclusion, LIGHT was upregulated in more malignant gliomas including glioblastoma, IDH wildtype, and mesenchymal subtype. LIGHT was mainly involved in the immune function of macrophages, T cells, and APCs and served as an independent prognosticator in glioma.

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“…Cancer is considered to be a disease of tumor microenvironment [26]. [28][29][30]. For example, cyclic actin promotes gastric cancer progression through sponge miRNA-331-3p and regulation of TGFBR1 mRNA expression [28].…”

Section: The Expression Level Of Cbll1 Is Related To Immunomodulatorsmentioning

confidence: 99%

The Role of M6A-related CBLL1 in the Prognosis and Immune Infiltration of Pan-cancer

Guo¹,

Li²,

Ji³

et al. 2020

Preprint

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Abstract Background The modification of N6-methyladenosine (m6A) plays an important role in physiology and disease progression. The relationship between the role of m6a-related gene CBLL1 in pan-carcinoma and tumor immune infiltrates has remained unknown. Methods To explore the expression level of CBLL1 methylation in pan-cancer in SMART database, and download mRNA expression, mutation and clinical data in UCSC database, to analyze the expression level of CBLL1, and the relationship between CBLL1 expression and clinicopathological features, prognosis, mutation and immune microenvironment in pan-cancer. CIBERSORT was used to analyze the relationship between the expression of CBLL1 and the infiltration of pan-carcinoma immune cells. The mRNA expression data of UCSC database were used to analyze the correlation between CBLL1 expression and pan-cancer immunomodulations, checkpoints and receptor molecules. Gene Set enrichment analysis (GSEA) revealed the possible mechanism of CBLL1 in the regulation of pan-cancer progression. Results The levels of CBLL1 methylation and mRNA expression in pan-cancer tissues were abnormal. The level of CBLL1 is related to the age, race, clinical stage and treatment effect of patients with pan-carcinoma and associated with the prognosis of patients with KIRC, LUSC, THCA, THYM, MESO, PRAD, STAD, and UVM. Univariate COX regression analysis showed that expression of CBLL1 was a risk factor for poor prognosis in patients with KICH, KIRC, LAML, THYM, KIRC, PCPG, OV, PRAD, STAD, GBM and UVM.The expression level of CBLL1 was correlated with BLCA, BRCA, COAD, LAML, LGG, LUAD, LUSC, SARC, STAD, THCA, THYM and UVM tumor mutational burden (TMB), and with ACC, BRCA, CESC, COAD, DLBC, HNSC, PRAD, READ, SARC, STAD, TGCT, THCA and UCEC microsatellite instability (MSI). The expression level of CBLL1 was correlated with pan-cancer stromal cells and immune cells. The expression of CBLL1 is related to pan-cancer immunomodulators, checkpoints and receptor molecules. GSEA found that CBLL1 may participate in the progression of pan-cancer through B cell receptor singaling pathway, mRNA binding, immunoglobulin receptor binding, Positive Regulation of cell cycle phase transition and other mechanisms. Conclusions CBLL1 is abnormally expressed in patients with pan-carcinoma, which is expected to be a biomarker for prognosis, mutation and immune infiltration in patients with pan-carcinoma.

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

Cited by 18 publications

References 45 publications

A novel Foxp3-related immune prognostic signature for glioblastoma multiforme based on immunogenomic profiling

A novel Foxp3-related immune prognostic signature for glioblastoma multiforme based on immunogenomic profiling

Molecular and Clinical Characterization of LIGHT/TNFSF14 Expression at Transcriptional Level via 998 Samples With Brain Glioma

The Role of M6A-related CBLL1 in the Prognosis and Immune Infiltration of Pan-cancer

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