Integrative Analysis of DNA Methylation and Transcriptome Identifies a Predictive Epigenetic Signature Associated With Immune Infiltration in Gliomas

Zhang, Jianlei; Jiang, Yin; Luo, Li; Huang, Dongzhou; Zhai, Dongfeng; Wang, Ge; Xu, Ning; Yang, Minqiang; Song, Ying; Zheng, Guopei; Zhang, Qiong

doi:10.3389/fcell.2021.670854

Cited by 7 publications

(5 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Different immune infiltrations can lead to different outcomes in tumors (43,44). For example, activated CD4 + memory T cell infiltration has been shown to be associated with poor prognosis and immune therapy response in several cancers (45,46), as have activated mast cells (47)(48)(49). This indicates that SLC2A1 might play a vital role in regulating the tumor immune microenvironment, and affects the prognosis of tumors by regulating infiltrating immune cells.…”

Section: Discussionmentioning

confidence: 99%

SLC2A1 plays a significant prognostic role in lung adenocarcinoma and is associated with tumor immunity based on bioinformatics analysis

Wang¹,

Wen²,

Sun³

2022

Ann Transl Med

View full text Add to dashboard Cite

Background The treatment of lung adenocarcinoma (LUAD) has been stuck in a bottleneck due to a number of factors. There is a pressing need for research into potential genetic markers to help drug development and improve the prognosis of patients. SLC2A1 has been reported in multiple LUAD-related prognosis prediction signatures . However, the role of SLC2A1 in the occurrence and development of LUAD and its impact on prognosis remain elusive. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were used to acquire the samples. We used R to perform statistical analysis, Gene Set Enrichment Analysis (GSEA), immune infiltration and immune cell correlation analysis, drug sensitivity analysis, and visualization. The immune cell score was calculated using the Timer2.0 database. Prognostic analysis was performed using R, Gene Expression Profiling Interactive Analysis (GEPIA), and the Kaplan-Meier Plotter. Overall survival and progression free survival were the main outcome of prognosis analysis. Protein-protein interaction, disease-genetics analysis, and tissue-specific enrichment analyses were performed using Metascape. Results SLC2A1 was highly expressed in LUAD tissues. Univariate COX regression [hazard ratio (HR) =1.689, 95% confidence interval (CI): 1.242–2.249, P<0.001] and multivariate COX regression including age, gender, smoking, TNM stage and SLC2A1 expression (HR =1.567, 95% CI: 1.127–2.179, P=0.008) showed that SLC2A1 was an independent prognostic risk factor for LUAD. GSEA and Metascape analysis showed that SLC2A1 was strongly associated with the cell cycle, mitosis, lung tissue, and tumor recurrence. Immune correlation analysis showed that SLC2A1 was associated with two tumor infiltration immune cells: activated CD (cluster of differentiation)4 + memory T cells (r=0.31, P=0.003) and activated mast cells (r=−0.28, P=0.010). Moreover, patients with high SLC2A1 expression had higher immune checkpoint molecules and Tumor Immune Dysfunction and Exclusion (TIDE) scores, indicating poorer immunotherapy efficacy. Patients with high SLC2A1 expression were more sensitive to chemotherapy drugs and less sensitive to targeted drugs compared to those with low SLC2A1 expression. Conclusions The high expression of SLC2A1 in LUAD predicted poor prognosis and was closely related to tumor immunity, which could be used as an effective prognostic biomarker to provide a new strategy for clinical prognosis assessment and immunotherapy for LUAD.

show abstract

Section: Discussionmentioning

confidence: 99%

SLC2A1 plays a significant prognostic role in lung adenocarcinoma and is associated with tumor immunity based on bioinformatics analysis

Wang¹,

Wen²,

Sun³

2022

Ann Transl Med

View full text Add to dashboard Cite

show abstract

“…Inflammatory characteristics are low in IDH-O, but progressively increase in IDH-A in the order E4-E3-E2 which associate with senescence and treatment resistance characteristics, decaying GCIMP-methylation and worse prognosis [20]. Recent studies developed risk scores related to DNA methylation and inflammatory tumor microenviroment resembling our characteristics [95,96].…”

Section: Combinations Of Proliferative Inflammatory and Tissue Remode...mentioning

confidence: 99%

High-Resolution Cartography of the Transcriptome and Methylome Landscapes of Diffuse Gliomas

Willscher

Hopp

Kreuz

et al. 2021

Cancers

View full text Add to dashboard Cite

Molecular mechanisms of lower-grade (II–III) diffuse gliomas (LGG) are still poorly understood, mainly because of their heterogeneity. They split into astrocytoma- (IDH-A) and oligodendroglioma-like (IDH-O) tumors both carrying mutations(s) at the isocitrate dehydrogenase (IDH) gene and into IDH wild type (IDH-wt) gliomas of glioblastoma resemblance. We generated detailed maps of the transcriptomes and DNA methylomes, revealing that cell functions divided into three major archetypic hallmarks: (i) increased proliferation in IDH-wt and, to a lesser degree, IDH-O; (ii) increased inflammation in IDH-A and IDH-wt; and (iii) the loss of synaptic transmission in all subtypes. Immunogenic properties of IDH-A are diverse, partly resembling signatures observed in grade IV mesenchymal glioblastomas or in grade I pilocytic astrocytomas. We analyzed details of coregulation between gene expression and DNA methylation and of the immunogenic micro-environment presumably driving tumor development and treatment resistance. Our transcriptome and methylome maps support personalized, case-by-case views to decipher the heterogeneity of glioma states in terms of data portraits. Thereby, molecular cartography provides a graphical coordinate system that links gene-level information with glioma subtypes, their phenotypes, and clinical context.

show abstract

“…In the training cohort, the AUC of our model for predicting 1-year and 2-year overall survival were higher than other models (F i g. 5 I). In addition, the accuracy of our model was also better than other glioma related models in the validation cohort 4 , 6 , 7 , 26 (Fig. 5 J).…”

Section: Resultsmentioning

confidence: 65%

Single cell RNA sequencing reveals differentiation related genes with drawing implications in predicting prognosis and immunotherapy response in gliomas

Zhou

Wei

Yang

et al. 2022

Sci Rep

View full text Add to dashboard Cite

Differentiation states of glioma cells correlated with prognosis and tumor-immune microenvironment (TIME) in patients with gliomas. We aimed to identify differentiation related genes (DRGs) for predicting the prognosis and immunotherapy response in patients with gliomas. We identified three differentiation states and the corresponding DRGs in glioma cells through single-cell transcriptomics analysis. Based on the DRGs, we separated glioma patients into three clusters with distinct clinicopathological features in combination with bulk RNA-seq data. Weighted correlation network analysis, univariate cox regression analysis and least absolute shrinkage and selection operator analysis were involved in the construction of the prognostic model based on DRGs. Distinct clinicopathological characteristics, TIME, immunogenomic patterns and immunotherapy responses were identified across three clusters. A DRG signature composing of 12 genes were identified for predicting the survival of glioma patients and nomogram model integrating the risk score and multi-clinicopathological factors were constructed for clinical practice. Patients in high-risk group tended to get shorter overall survival and better response to immune checkpoint blockage therapy. We obtained 9 candidate drugs through comprehensive analysis of the differentially expressed genes between the low and high-risk groups in the model. Our findings indicated that the risk score may not only contribute to the determination of prognosis but also facilitate in the prediction of immunotherapy response in glioma patients.

show abstract

Integrative Analysis of DNA Methylation and Transcriptome Identifies a Predictive Epigenetic Signature Associated With Immune Infiltration in Gliomas

Cited by 7 publications

References 55 publications

SLC2A1 plays a significant prognostic role in lung adenocarcinoma and is associated with tumor immunity based on bioinformatics analysis

SLC2A1 plays a significant prognostic role in lung adenocarcinoma and is associated with tumor immunity based on bioinformatics analysis

High-Resolution Cartography of the Transcriptome and Methylome Landscapes of Diffuse Gliomas

Single cell RNA sequencing reveals differentiation related genes with drawing implications in predicting prognosis and immunotherapy response in gliomas

Contact Info

Product

Resources

About