Profiles of immune‐related genes and immune cell infiltration in the tumor microenvironment of diffuse lower‐grade gliomas

e15236 Background: In recent years, cancer immunotherapy has been extensively studied, and colorectal cancer (CRC) patients have also derived clinical benefits from immunotherapy, especially CRC patients with mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H), whose sensitivity to immune checkpoint inhibitors (ICIs) is significantly higher than that of patients with microsatellite-stable (MSS)/microsatellite instability-low (MSI-L) disease. This study suggests that patients with MSI-H CRC have a higher mutational burden and more immune cell infiltration than those with MSS/MSI-L disease. However, most studies have not systematically evaluated the immune characteristics and immune microenvironments of MSI-H and MSS/MSI-L CRC. Methods: A published CRC cohort with mutation and immunotherapy-related prognostic data was collected. We analyzed the relationship between the MSI status and prognosis of ICI treatment in an immunotherapy cohort. We then further used mutation data for the immunotherapy and The Cancer Genome Atlas (TCGA)-CRC (colon adenocarcinoma (COAD) + rectum adenocarcinoma (READ) cohorts. For mRNA expression, mutation data analysis of the immune microenvironment and immunogenicity under different MSI status was performed. Results: Compared with MSS/MSI-L CRC patients, patients with MSI-H CRC significantly benefited from ICI treatment. We found that MSI-H CRC had more immune cell infiltration, higher expression of immune-related genes and higher immunogenicity than MSS/MSI-L disease. The MANTIS score used to predict the MSI status was positively correlated with immune cells, immune-related genes, and immunogenicity. In addition, subtype analysis showed that COAD and READ might have different tumor immune microenvironments. Conclusions: MSI-H CRC may have an inflammatory tumor microenvironment and increased sensitivity to ICIs. Unlike those of MSI-H READ, the immune characteristics of MSI-H COAD may be consistent with those of MSI-H CRC. Furthermore, the possible mechanism underlying the prognostic differences among CRC patients receiving ICIs in relation to the immune microenvironment were elucidated to provide theoretical guidance for further improving the curative effect of ICIs treatment on MSI-H CRC patients in the future and solve the problems underlying why MSS/MSI-L CRC patients do not benefit from ICIs treatment.

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Profiles of immune cell infiltration and immune-related genes in the tumor microenvironment of osteosarcoma

Aging ◽

10.18632/aging.102824 ◽

2020 ◽

Vol 12 (4) ◽

pp. 3486-3501 ◽

Cited By ~ 11

Author(s):

Chi Zhang ◽

Jing-Hui Zheng ◽

Zong-Han Lin ◽

Hao-Yuan Lv ◽

Zhuo-Miao Ye ◽

...

Keyword(s):

Tumor Microenvironment ◽

Immune Cell ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Immune Related Genes

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Development of an Immune-Related Gene Signature for Prognosis in Melanoma

Frontiers in Oncology ◽

10.3389/fonc.2020.602555 ◽

2021 ◽

Vol 10 ◽

Author(s):

Jia-An Zhang ◽

Xu-Yue Zhou ◽

Dan Huang ◽

Chao Luan ◽

Heng Gu ◽

...

Keyword(s):

T Cells ◽

Immune Cell ◽

Treatment Method ◽

Gene Signature ◽

Cell Infiltration ◽

Venn Diagram ◽

Immune Cell Infiltration ◽

Tumor Purity ◽

New Treatment ◽

Immune Related Genes

Melanoma remains a potentially deadly malignant tumor. The incidence of melanoma continues to rise. Immunotherapy has become a new treatment method and is widely used in a variety of tumors. Original melanoma data were downloaded from TCGA. ssGSEA was performed to classify them. GSVA software and the "hclust" package were used to analyze the data. The ESTIMATE algorithm screened DEGs. The edgeR package and Venn diagram identified valid immune-related genes. Univariate, LASSO and multivariate analyses were used to explore the hub genes. The "rms" package established the nomogram and calibrated the curve. Immune infiltration data were obtained from the TIMER database. Compared with that of samples in the high immune cell infiltration cluster, we found that the tumor purity of samples in the low immune cell infiltration cluster was higher. The immune score, ESTIMATE score and stromal score in the low immune cell infiltration cluster were lower. In the high immune cell infiltration cluster, the immune components were more abundant, while the tumor purity was lower. The expression levels of TIGIT, PDCD1, LAG3, HAVCR2, CTLA4 and the HLA family were also higher in the high immune cell infiltration cluster. Survival analysis showed that patients in the high immune cell infiltration cluster had shorter OS than patients in the low immune cell infiltration cluster. IGHV1-18, CXCL11, LTF, and HLA-DQB1 were identified as immune cell infiltration-related DEGs. The prognosis of melanoma was significantly negatively correlated with the infiltration of CD4+ T cells, CD8+ T cells, dendritic cells, neutrophils and macrophages. In this study, we identified immune-related melanoma core genes and relevant immune cell subtypes, which may be used in targeted therapy and immunotherapy of melanoma.

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Association Between Tumor Mutation Burden and Prognosis in Lower-Grade Glioma: An Exploratory Study

10.21203/rs.3.rs-137165/v1 ◽

2021 ◽

Author(s):

Di Cao ◽

Jun Wang ◽

Yan Lin ◽

Guangwei Li

Keyword(s):

Immune Cell ◽

Differential Expression Analysis ◽

Cell Infiltration ◽

Lower Grade ◽

Immune Cell Infiltration ◽

Hub Genes ◽

Tumor Mutation Burden ◽

Mutation Burden ◽

Lower Grade Glioma ◽

Genome Atlas

Abstract Background: The therapeutic efficacy of immune checkpoint inhibitor therapy is highly influenced by tumor mutation burden (TMB). The relationship between TMB and prognosis in lower-grade glioma is still unclear. We aimed to explore the relationships and mechanisms between them in lower-grade glioma.Methods: We leveraged somatic mutation data from The Cancer Genome Atlas (TCGA). Clinical cases were divided into high- and low-TMB groups based on the median of TMB. Infiltrating immune cells were analyzed using CIBERSORT and differential expression analysis between the prognostic groups performed. The key genes were identified as intersecting between immune-related genes. Cox regression and survival analysis were performed on the intersecting genes. A total of 7 hub genes were identified. The effect of somatic copy number alterations (SCNA) of the hub genes on immune cell infiltration was analyzed using TIMER, which was used to determine the risk factors and immune infiltration status in LGG. Subsequently, based on hub genes, a TMB Prognosis Index (TMBPI) model was constructed to predict the risk in LGG patients. Besides, this model was validated using data from TCGA and Chinese Glioma Genome Atlas (CGGA).Results: High-TMB favored worse prognosis (P＜0.001) and macrophage infiltration was an independent risk factor (P＜0.001). In the high-TMB group (P=0.033, P=0.009), the proportion of macrophages M0 and M2 increased and monocytes decreased (P=0.006). Besides, the SCNA of the hub genes affected the level of immune cell infiltration by varying degrees among which IGF2BP3, NPNT, and PLA2G2A had a significant impact. The AUC of the ROC curve at 1-, 3- and 5-years were all above 0.74.Conclusions: This study implies that high-TMB correlated with unfavorable prognosis in lower-grade glioma. And high-TMB may have an impact on prognosis by changing tumor microenvironment, caused by the SCNAs of genes. The TMBPI model accurately predicted prognosis in LGG patients.

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Glucose-6-Phosphate Dehydrogenase is a Prognostic Biomarker and Correlated with Immune Infiltrates in Hepatocellular Carcinoma

10.21203/rs.3.rs-1232206/v1 ◽

2022 ◽

Author(s):

Yang Bu ◽

Kejun Liu ◽

Yiming Niu ◽

Ji Hao ◽

Lei Cui ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Microenvironment ◽

Liver Cancer ◽

Immune Cell ◽

Cox Regression ◽

Functional Enrichment ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Potential Biomarker ◽

Glucose 6 Phosphate Dehydrogenase

Abstract Background: Glucose-6-phosphate dehydrogenase (G6PD) plays an important role in the metabolic and immunological aspects of tumors. In hepatocellular carcinoma (HCC), the alteration of tumor microenvironment influences recurrence and metastasis. We extracted G6PD-related data from public databases of HCC tissues and used a bioinformatics approach to explore the correlation between G6PD expression and clinicopathological features and prognosis of immune cell infiltration in HCC.Methods: We extract G6PD expression information from TCGA and GEO databases in liver cancer tissues and normal tissues, validated by immunohistochemistry, and the correlation between G6PD expression and clinical features is analyzed, and the clinical significance of G6PD in liver cancer is assessed by Kaplan-Meier, Cox regression and prognostic line graph models. Functional enrichment analysis is performed by protein-protein interaction (PPI) network, GO/KEGG, GSEA and G6PD-associated differentially expressed genes (DEGs). TIMER and ssGSEA packages are used to assess the correlation between expression and the level of immune cell infiltration.Results: Our results show that G6PD expression is significantly upregulated in hepatocellular carcinoma tissues (P < 0.001). G6PD expression is associated with histological grade, pathological stage, T-stage, vascular infiltration and AFP level (P < 0.05); HCC patients in the low G6PD expression group had longer overall survival and better prognosis compared with the high G6PD expression group (P < 0.05). The level of G6PD expression also affects the levels of macrophages, unactivated dendritic cells, B cells, and follicular helper T cells in the tumor microenvironment.Conclusion: High expression of G6PD is a potential biomarker for poor prognosis of hepatocellular carcinoma, and G6PD may be a target for immunotherapy of HCC.

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Tumor Mutation Burden, Immune Cell Infiltration, and Construction of Immune-Related Genes Prognostic Model in Head and Neck Cancer

International Journal of Medical Sciences ◽

10.7150/ijms.51064 ◽

2021 ◽

Vol 18 (1) ◽

pp. 226-238

Author(s):

Ai-Min Jiang ◽

Meng-Di Ren ◽

Na Liu ◽

Huan Gao ◽

Jing-Jing Wang ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Prognostic Model ◽

Immune Cell ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Tumor Mutation Burden ◽

Mutation Burden ◽

Immune Related Genes

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Identification and Validation of Immune-Related Genes and Immune Cell Infiltration in Preeclampsia

10.21203/rs.3.rs-1152649/v1 ◽

2021 ◽

Author(s):

Rongxin Chen ◽

Qing Han ◽

Huale Zhang ◽

Jianying Yan

Keyword(s):

Immune Cell ◽

Risk Model ◽

Differentially Expressed ◽

Cell Infiltration ◽

Receptor Interaction ◽

Immune Cell Infiltration ◽

Multisystem Disease ◽

Predicting Model ◽

Immune Related Genes ◽

Maternal Fetal Interface

Abstract Background Preeclampsia (PE) is a complex multisystem disease and its etiology remains unclear. The aim of this study was to identify potential immune-related diagnostic genes for PE, analyze the role of immune cell infiltration in PE, and explore the mechanism underlying PE-induced disruption of immune tolerance at the maternal-fetal interface. Methods We used the PE dataset GES25906 from Gene Expression Omnibus and immune-related genes from ImmPort database. The differentially expressed genes (DEGs) were identified using the “limma” package, and the differentially expressed immune-related genes (DEIGs) were extracted from the DEGs and immune-related genes using Venn diagrams. The potential functions of DEIGs were determined by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Furthermore, the protein–protein interaction network was obtained from the STRING database, and it was visualized using Cytoscape software. Least absolute shrinkage and selection operator logistic regression was used to verify the diagnostic markers of PE and build a predicting model. The model was validated using datasets GSE66273 and GSE75010. Finally, CIBERSORT was used to evaluate the infiltration of immune cells in PE tissues. Results Six genes (ACTG1, ENG, IFNGR1, ITGB2, NOD1, and SPP1) enriched in Th17 cell differentiation, cytokine-cytokine receptor interaction, innate immune response, and positive regulation of MAPK cascade pathways were identified, and a predicting model was built. Datasets GSE66273 and GSE75010 were used to validate the model, and the area under the curve was 0.8333 and 0.8107, respectively. Immune cell infiltration analysis revealed an increase in plasma cells and gamma delta T cells and a decrease in resting natural killer cells in the high score group according to the predictive model risk values. Conclusions We developed a risk model to predict PE and proved that immune imbalance at the maternal-fetal interface plays a key role in the pathogenesis of PE.

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Molecular Characterization of the Clinical and Tumor Immune Microenvironment Signature of 5-methylcytosine-Related Regulators in non-small Cell Lung Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.779367 ◽

2021 ◽

Vol 9 ◽

Author(s):

Taisheng Liu ◽

Liyi Guo ◽

Guihong Liu ◽

Xiaoshan Hu ◽

Xiaoning Li ◽

...

Keyword(s):

Lung Cancer ◽

Tumor Microenvironment ◽

Immune Cell ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Check Point ◽

Clinical Prognosis ◽

Tumor Mutation Burden ◽

Mutation Burden ◽

Immune Check Point Inhibitor

Background: DNA methylation is an important epigenetic modification, among which 5-methylcytosine methylation (5mC) is generally associated with tumorigenesis. Nonetheless, the potential roles of 5mC regulators in the tumor microenvironment (TME) remain unclear.Methods: The 5mC modification patterns of 1,374 lung adenocarcinoma samples were analyzed systematically. The correlation between the 5mC modification and tumor microenvironment cell infiltration was further assessed. The 5mCscore was developed to evaluate tumor mutation burden, immune check-point inhibitor response, and the clinical prognosis of individual tumors.Results: Three 5mC modification patterns were established based on the clinical characteristics of 21 5mC regulators. According to the differential expression of 5mC regulators, three distinct 5mC gene cluster were also identified, which showed distinct TME immune cell infiltration patterns and clinical prognoses. The 5mCscore was constructed to evaluate the tumor mutation burden, immune check-point inhibitor response, and prognosis characteristics. We found that patients with a low 5mCscore had significant immune cell infiltration and increased clinical benefit.Conclusion: This study indicated that the 5mC modification is involved in regulating TME infiltration remodeling. Targeting 5mC modification regulators might be a novel strategy to treat lung cancer.

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