Uncovering the Immune Cell Infiltration Landscape in Low-Grade Glioma for Aiding Immunotherapy

Yang, Youyuan; Tian, Yongji; Li, Qing; Jiang, Rui; Zhang, Junfeng

doi:10.1155/2022/3370727

Cited by 10 publications

(6 citation statements)

References 39 publications

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“…CD8 + T cells were essential for T cell-mediated tumor control and could release more predictive ICI-related biomarkers, such as PD-1 and PD-L1 [ 47 ]. Yang et al constructed an ICI score based on 22 immune cells and ascertained that higher eosinophils were in the high-ICI LGG patients who had a worse prognosis [ 48 ]. Furthermore, we used several immune infiltrating methods to ensure the stability of our results on the basis of these results above.…”

Section: Discussionmentioning

confidence: 99%

Development of a Hallmark Pathway-Related Gene Signature Associated with Immune Response for Lower Grade Gliomas

Lai

Zhong

Liu

et al. 2022

IJMS

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Although some biomarkers have been used to predict prognosis of lower-grade gliomas (LGGs), a pathway-related signature associated with immune response has not been developed. A key signaling pathway was determined according to the lowest adjusted p value among 50 hallmark pathways. The least absolute shrinkage and selection operator (LASSO) and stepwise multivariate Cox analyses were performed to construct a pathway-related gene signature. Somatic mutation, drug sensitivity and prediction of immunotherapy analyses were conducted to reveal the value of this signature in targeted therapies. In this study, an allograft rejection (AR) pathway was considered as a crucial signaling pathway, and we constructed an AR-related five-gene signature, which can independently predict the prognosis of LGGs. High-AR LGG patients had higher tumor mutation burden (TMB), Immunophenscore (IPS), IMmuno-PREdictive Score (IMPRES), T cell-inflamed gene expression profile (GEP) score and MHC I association immunoscore (MIAS) than low-AR patients. Most importantly, our signature can be validated in four immunotherapy cohorts. Furthermore, IC50 values of the six classic chemotherapeutic drugs were significantly elevated in the low-AR group compared with the high-AR group. This signature might be regarded as an underlying biomarker in predicting prognosis for LGGs, possibly providing more therapeutic strategies for future clinical research.

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Section: Discussionmentioning

confidence: 99%

Development of a Hallmark Pathway-Related Gene Signature Associated with Immune Response for Lower Grade Gliomas

Lai

Zhong

Liu

et al. 2022

IJMS

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“…Another research established an immune-related radiosensitivity prognostic signature that could effectively predict the prognosis of LGG patients receiving radiotherapy (Yan et al, 2022). Studies have identified immune-related subsets in diffuse glioma (Zhou et al, 2020), LGG (Yang et al, 2022), and isocitrate dehydrogenase (IDH) wild-type LGG (Wu et al, 2020), which provided potential immunotherapy targets for different types of glioma. Wang et al (2021) found that REXO2 and RUNX1 contributed to the heterogeneity and prognosis of the IDH wild-type LGG.…”

Section: Introductionmentioning

confidence: 99%

Integrated analysis of inflammatory response subtype-related signature to predict clinical outcomes, immune status and drug targets in lower-grade glioma

Cao

Zhu²,

Chen

et al. 2022

Front. Pharmacol.

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Background: The inflammatory response in the tumor immune microenvironment has implications for the progression and prognosis in glioma. However, few inflammatory response-related biomarkers for lower-grade glioma (LGG) prognosis and immune infiltration have been identified. We aimed to construct and identify the prognostic value of an inflammatory response-related signature, immune infiltration, and drug targets for LGG.Methods: The transcriptomic and clinical data of LGG samples and 200 inflammatory response genes were obtained from public databases. The LGG samples were separated into two inflammatory response-related subtypes based on differentially expressed inflammatory response genes between LGG and normal brain tissue. Next, inflammatory response-related genes (IRRGs) were determined through a difference analysis between the aforementioned two subtypes. An inflammatory response-related prognostic model was constructed using IRRGs by using univariate Cox regression and Lasso regression analyses and validated in an external database (CGGA database). ssGSEA and ESTIMATE algorithms were conducted to evaluate immune infiltration. Additionally, we performed integrated analyses to investigate the correlation between the prognostic signature and N 6-methyladenosine mRNA status, stemness index, and drug sensitivity. We finally selected MSR1 from the prognostic signature for further experimental validation.Results: A total of nine IRRGs were identified to construct the prognostic signature for LGG. LGG patients in the high-risk group presented significantly reduced overall survival than those in the low-risk group. An ROC analysis confirmed the predictive power of the prognostic model. Multivariate analyses identified the risk score as an independent predictor for the overall survival. ssGSEA revealed that the immune status was definitely disparate between two risk subgroups, and immune checkpoints such as PD-1, PD-L1, and CTLA4 were significantly expressed higher in the high-risk group. The risk score was strongly correlated with tumor stemness and m6A. The expression levels of the genes in the signature were significantly associated with the sensitivity of tumor cells to anti-tumor drugs. Finally, the knockdown of MSR1 suppressed LGG cell migration, invasion, epithelial–mesenchymal transition, and proliferation.Conclusion: The study constructed a novel signature composed of nine IRRGs to predict the prognosis, potential drug targets, and impact immune infiltration status in LGG, which hold promise for screening prognostic biomarkers and guiding immunotherapy for LGG.

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“…Macrophage infiltration was significantly increased in the high-risk group in this study, which may have contributed to the poor prognosis of the high-risk group. In a study revealing immune cell infiltration and immunotherapy in low-grade gliomas, high immune infiltration scores were significantly associated with increased levels of CD4 naïve T cell infiltration, and high CD4 naïve T cell expression suggested a good prognosis for patients ( 30 ). DEGIn addition, Altered somatic Mitochondrial DNA (mtDNA) or low mtDNA copy number promotes cancer progression and metastasis by activating retrograde mitochondrial signalling ( 31 , 32 ).…”

Section: Discussionmentioning

confidence: 99%

Novel prognostic features and personalized treatment strategies for mitochondria-related genes in glioma patients

Zhou

Chai

et al. 2023

Front. Endocrinol.

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BackgroundGliomas are the most common intracranial nervous system tumours that are highly malignant and aggressive, and mitochondria are an important marker of metabolic reprogramming of tumour cells, the prognosis of which cannot be accurately predicted by current histopathology. Therefore, Identify a mitochondrial gene with immune-related features that could be used to predict the prognosis of glioma patients.MethodsGliomas data were downloaded from the TCGA database and mitochondrial-associated genes were obtained from the MITOCARTA 3.0 dataset. The CGGA, kamoun and gravendeel databases were used as external datasets. LASSO(Least absolute shrinkage and selection operator) regression was applied to identify prognostic features, and area and nomograms under the ROC(Receiver Operating Characteristic) curve were used to assess the robustness of the model. Single sample genomic enrichment analysis (ssGSEA) was employed to explore the relationship between model genes and immune infiltration, and drug sensitivity was used to identify targeting drugs. Cellular studies were then performed to demonstrate drug killing against tumours.ResultsCOX assembly mitochondrial protein homolog (CMC1), Cytochrome c oxidase protein 20 homolog (COX20) and Cytochrome b-c1 complex subunit 7 (UQCRB) were identified as prognostic key genes in glioma, with UQCRB, CMC1 progressively increasing and COX20 progressively decreasing with decreasing risk scores. ROC curve analysis of the TCGA training set model yielded AUC (Area Under The Curve) values >0.8 for 1-, 2- and 3-year survival, and the model was associated with both CD8+ T cells and immune checkpoints. Finally, using cellMiner database and molecular docking, it was confirmed that UQCRB binds covalently to Amonafide via lysine at position 78 and threonine at position 82, while cellular assays showed that Amonafide inhibits glioma migration and invasion.ConclusionOur three mitochondrial genomic composition-related features accurately predict Survival in glioma patients, and we also provide glioma chemotherapeutic agents that may be mitochondria-related targets.

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Uncovering the Immune Cell Infiltration Landscape in Low-Grade Glioma for Aiding Immunotherapy

Cited by 10 publications

References 39 publications

Development of a Hallmark Pathway-Related Gene Signature Associated with Immune Response for Lower Grade Gliomas

Development of a Hallmark Pathway-Related Gene Signature Associated with Immune Response for Lower Grade Gliomas

Integrated analysis of inflammatory response subtype-related signature to predict clinical outcomes, immune status and drug targets in lower-grade glioma

Novel prognostic features and personalized treatment strategies for mitochondria-related genes in glioma patients

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