scholarly journals N6-Methyladenosine Related Long Non-Coding RNAs and Immune Cell Infiltration in the Tumor Microenvironment of Gastric Cancer

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Zhong lin Yu ◽  
Zheng ming Zhu
Keyword(s):  
Gastric Cancer ◽  
Tumor Microenvironment ◽  
Prognostic Model ◽  
Tumor Tissue ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Non Coding Rnas ◽  
The Relationship ◽  
Cluster 2

Abstract Aim To illustrate the influence of N6-methyladenosine long non-coding RNAs and immune cell infiltration in gastric cancer. Methods We downloaded workflow-type data and clinical data from The Cancer Genome Atlas project. The relationship of lncRNA and m6A was identified. Kyoto Encyclopedia of Genes and Genomes gene expression enrichment analysis was performed. Lasso regression was utilized to construct a prognostic model. Survival analysis to explore the relationship between m6A lncRNA and clinical survival data. Differential analysis of the tumor microenvironment and immune correlation analysis to determine immune cell infiltration levels and their correlation with clinical prognosis. Results Co-expression analysis indicated that lncRNA expression was associated closely with m6A. m6A-lncRNAs were partially highly expressed in tumor tissue and could be used in a prognostic model to predict GC prognosis, independent of other clinical characteristics. “ADIPPOCYTOKINE SIGNALING PATHWAY” was most significantly enriched according to GSEA. ACBD3-AS1 was overexpressed in tumor tissue. Naïve B cell, Plasma cells, resting CD4 memory T cell were highly infiltrated tissues in cluster 2, while Macrophages M2, resting Mast cells, Monocytes, regulates T cells were lowly in cluster 1. All related scores were higher in cluster 2, indicating a lower purity of tumor cells and higher density of immune-related cells in the tumor microenvironment. Conclusion m6A lncRNA is closely related to the occurrence and progression of GC. The corresponding prognostic model can be utilized to evaluate the prognosis of GC. m6A lncRNA and related immune cell infiltration in the tumor microenvironment can provide novel therapeutic targets for further research.

scholarly journals C3aR1 Correlates With Immune Cell Infiltration and Serves as Prognostic and Therapeutic Biomarker in Gastric Cancer

2021 ◽  
Author(s):  
weifeng liu ◽  
Zhijie Chu ◽  
Cheng Yang ◽  
Tianbao Yang ◽  
Yanhui Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cell ◽  
Differentially Expressed Genes ◽  
Tumor Tissue ◽  
Immune Cell ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Expression Levels

Abstract As the fourth most common malignancy worldwide, gastric cancer can lead more than 720 000 patient death every year. Precisely therapeutic intervention can significantly improve patients’ survival status underlying the precise clarification by molecular indexes. Identifying the biomarkers highly associated with disease prognosis will be helpful to guide the clinical therapy. C3ar1 is an essential receptor in the complement system, and participates in various biological processes associated with immunological responses. To identify the crucial roles of C3AR1 in gastric cancer tmorigenesis, we determined the mRNA profile, protein expression levels and the clinicopathological indexes using cBioportal, Kaplan-Meier plotter and the Human Protein Atlas databases. To identify the molecular network in C3AR1-expressed gastric cancer, we obtained the differentially expressed genes using the GEPIA database compared with normal stomach tissues. Furthermore, we analyzed the biological impact of these differentially expressed genes using protein-protein interaction network and gene set enrichment analysis, in which we identified the hub genes and critical pathways influenced by over-expressed C3AR1 in gastric cancer. Finally, we evaluated the correlation between the C3AR1 expression levels and immune cell infiltration levels utilizing the Tumor Immunoassay Resource database. Our results revealed that the higher expression level of C3AR1 can lead higher infiltration of T cell CD8+, T cell CD4+, macrophage, neutrophil, B cell and myeloid dendritic cells into tumor tissue. Moreover, we also found that higher infiltration of macrophage cells into tumor tissue can worsen the survival of patients with gastric cancer, which may be highly associated with the polarization states of macrophages (TAM and M2 status). Our investigation suggest that C3AR1 can be as an efficient diagnostic biomarkers for gastric cancer therapy.

scholarly journals Signatures Based On Tumor Microenvironment Genes Can Reliably Predict The Prognosis of Laryngeal Cancer Patients

2021 ◽  
Author(s):  
Haitang Ren ◽  
Zheng Luo ◽  
Min Wang ◽  
Lei Chen ◽  
Bo Zhang
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Patients ◽  
Laryngeal Cancer ◽  
Prognostic Model ◽  
Immune Cell ◽  
Low Risk ◽  
Cell Infiltration ◽  
Immune Checkpoints ◽  
Immune Cell Infiltration ◽  
Significant Difference

Abstract Purpose: To develop a tumor microenvironment (TME) related genes based prognostic model for laryngeal cancer patients risk prediction. Methods: A innovative prognosic model was generated based on TME related genes (760 genes). Based on the model, laryngeal cancer patients were categoried into high and low-risk group. The immune status including immune cell infiltration ratio as well as checkpoints have been exploreds.Results: It can be shown here 15 genes demonstrate significant differences, which can better predict laryngeal cancer patient prognosis. The accuracy of the model prediction is evaluated and approved by the AUC value. From the immune cell infiltration ratio analysis, there is a significant difference in the infiltration degree of several types of immune cells and 6 immune checkpoints between high and low-risk laryngeal cancer patients. At the same time, the close related genes as well as TME pathways have been also investigated.Conclusion: This study has explored a potential prognostic biomarker and developed a novel TME-associated prognostic model for laryngeal cancer, which provides a valuable reference for future clinical research.

scholarly journals Identification of Stemness Characteristics Associated With the Immune Microenvironment and Prognosis in Gastric Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Deli Mao ◽  
Zhijun Zhou ◽  
Shenglei Song ◽  
Dongsheng Li ◽  
Yulong He ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Microenvironment ◽  
Gene Mutation ◽  
Clinical Characteristics ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Survival Prediction ◽  
Immune Cell Infiltration ◽  
Prognostic Signature ◽  
Mutation Status

BackgroundGastric cancer (GC) is a highly heterogeneous disease. In recent years, the prognostic value of the mRNA expression-based stemness index (mRNAsi) across cancers has been reported. We intended to identify stemness index-associated genes (SI-genes) for clinical characteristic, gene mutation status, immune response, and tumor microenvironment evaluation as well as risk stratification and survival prediction.MethodsThe correlations between the mRNAsi and GC prognosis, clinical characteristics, gene mutation status, immune cell infiltration and tumor microenvironment were evaluated. Weighted gene correlation network analysis (WGCNA) was performed to identify SI-genes from differentially expressed genes (DEGs) in The Cancer Genome Atlas (TCGA). Single-sample gene set enrichment analysis (ssGSEA) was employed to calculate the sample SI-gene-based ssGSEA score according to the SI-genes. Then, the correlations between the ssGSEA score and GC prognosis, clinical characteristics, gene mutation status, immune cell infiltration and tumor microenvironment were analyzed. Finally, the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was used to construct a prognostic signature with prognostic SI-genes. The ssGSEA score and prognostic signature were validated using the Gene Expression Omnibus (GEO) database.ResultsThe mRNAsi could predict overall survival (OS), clinical characteristics, the gene mutation status, immune cell infiltration, and the tumor microenvironment composition. Fourteen positive SI-genes and 178 negative SI-genes were screened out using WGCNA. The ssGSEA score, similar to the mRNAsi, was found to be closely related to OS, clinical characteristics, the gene mutation status, immune cell infiltration, and the tumor microenvironment composition. Finally, a prognostic signature based on 18 prognostic SI-genes was verified to more accurately predict GC 1-year, 3-year, and 5-year OS than traditional clinical prediction models.ConclusionThe ssGSEA score and prognostic signature based on 18 prognostic SI-genes are of great value for immune response evaluation, risk stratification and survival prediction in GC and suggest that stemness features are crucial drivers of GC progression.

scholarly journals Signatures based on tumor microenvironment genes can reliably predict the prognosis of laryngeal cancer patients

2021 ◽  
Author(s):  
Haitang Ren ◽  
Zheng Luo ◽  
Min Wang ◽  
Lei Chen ◽  
Bo Zhang
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Patients ◽  
Laryngeal Cancer ◽  
Prognostic Model ◽  
Immune Cell ◽  
Low Risk ◽  
Cell Infiltration ◽  
Immune Checkpoints ◽  
Immune Cell Infiltration ◽  
Significant Difference

Abstract Purpose: To develop a tumor microenvironment (TME) related genes based prognostic model for laryngeal cancer patients risk prediction. Methods: A innovative prognosic model was generated based on TME related genes (760 genes). Based on the model, laryngeal cancer patients were categoried into high and low-risk group. The immune status including immune cell infiltration ratio as well as checkpoints have been exploreds. Results: It can be shown here 15 genes demonstrate significant differences, which can better predict laryngeal cancer patient prognosis. The accuracy of the model prediction is evaluated and approved by the AUC value. From the immune cell infiltration ratio analysis, there is a significant difference in the infiltration degree of several types of immune cells and 6 immune checkpoints between high and low-risk laryngeal cancer patients. At the same time, the close related genes as well as TME pathways have been also investigated. Conclusion: This study has explored a potential prognostic biomarker and developed a novel TME-associated prognostic model for laryngeal cancer, which provides a valuable reference for future clinical research.

scholarly journals Comprehensive Analysis of Pyroptosis-Related Genes and Tumor Microenvironment Infiltration Characterization in Breast Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
JianBin Wu ◽  
Yuanyuan Zhu ◽  
MingMin Luo ◽  
Lei Li
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Immune Checkpoint ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Clinical Prognosis ◽  
The Relationship ◽  
Single Tumor

BackgroundImmunotherapy has emerged as a significant strategy to treat numerous tumors. The positive response to immunotherapy depends on the dynamic interaction between tumor cells and infiltrating lymphocytes in the tumor microenvironment (TME). Pyroptosis, inflammation-induced cell death, is intricately associated with several tumors. However, the relationship between pyroptosis and clinical prognosis, immune cell infiltration, and immunotherapy effect is unclear in breast cancer (BRCA).MethodsWe comprehensively evaluated 33 pyroptosis-related genes and systematically assessed the relationship between pyroptosis and tumor progression, prognosis, and immune cell infiltration. The PyroptosisScore was used to quantify the pyroptosis pattern of a single tumor patient. We then assessed their values for predicting prognoses and therapeutic responses in BRCA.ResultsThree different modes of PyroptosisClusters were determined. The characteristics of TME cell infiltration in these three PyroptosisClusters were highly consistent with three immunophenotypes of tumors, including immune-excluded, immune-inflamed, and immune-desert phenotypes. Comprehensive bioinformatics analysis revealed that patients with a low PyroptosisScore had higher immune checkpoint expression, higher immune checkpoint inhibitor (ICI) scores, increased immune microenvironment infiltration, and were more sensitive to immunotherapy than those with a high PyroptosisScore.ConclusionsOur findings revealed the crucial role of pyroptosis in maintaining the diversity and complexity of TME. Pyroptosis is closely related to tumor progression, tumor prognosis, and immunotherapy response. Evaluating the PyroptosisScore of a single tumor can assist in understanding the characteristics of TME infiltration and lead to the development of more effective immunotherapy strategies.

scholarly journals AEBP1 Predicts Clinical Prognosis and is Associated with Immunocyte Infiltration in Gastric Cancer

2021 ◽  
Author(s):  
Junsheng Deng ◽  
Ting Zhan ◽  
Xiaoli Chen ◽  
Yiyuan Wan ◽  
Mengge Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Immune Cell ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Cell Infiltration ◽  
Gene Marker ◽  
Immune Cell Infiltration ◽  
Clinical Prognosis ◽  
The Relationship

Abstract AEBP1 is differentially expressed in various tumors. However, the correlation between AEBP1 and immune cell infiltration in gastric cancer remains unclear. Kaplan-Meier survival curves were used to evaluate the relationship between AEBP1 expression and overall survival and progression-free survival. The relationship between AEBP1 expression and infiltrating immune cells, and their corresponding gene marker sets was examined using the TIMER database.The expression of AEBP1 was lower in gastric cancer (GC) tumor tissues than in normal tissues (P < 0.05). High AEBP1 gene expression and high levels of AEBP1 gene methylation were correlated with high-grade malignant tumor and old TNM stage. In addition, in gastric cancer, there was a positive correlation between AEBP1 expression and immune infiltrating cells, including neutrophils, CD8 + T cells, and CD4 + T cells, as well as immune-related genes, including CD2, CD3D, and CD3E. Methylation sites such as cg00009293, cg08495088, cg12955216, cg10480062, cg06852744 and cg12978582 were positively correlated with low expression of AEBP1. AEBP1 may be a potential tumor suppressor gene in GC and a potential novel therapeutic target and predictive biomarker for GC. AEBP1 likely plays an important role in immune cell infiltration.

scholarly journals m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in Hepatocarcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Jianhao Li ◽  
Weiwei Wang ◽  
Yubing Zhou ◽  
Liwen Liu ◽  
Guizhen Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Clinical Features ◽  
Poor Prognosis ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
T Cell Infiltration ◽  
The Relationship

Background: Immunotherapy elicits durable responses in many tumors. Nevertheless, the positive response to immunotherapy always depends on the dynamic interactions between the tumor cells and infiltrating lymphocytes in the tumor microenvironment (TME). Currently, the application of immunotherapy in hepatocellular carcinoma (HCC) has achieved limited success. The ectopic modification of N6-methyladenosine (m6A) is a common feature in multiple tumors. However, the relationship between m6A modification with HCC clinical features, prognosis, immune cell infiltration, and immunotherapy efficacy remains unclear.Materials and Methods: Here, we comprehensively evaluated m6A modification clusters based on 22 m6A regulators and systematically explored the relationship between m6A modification with tumor progression, prognosis, and immune cell infiltration characteristics. The m6Ascore was calculated by principal component analysis to quantify the m6A modifications of individual patients. Key regulators involved in immunoregulation in HCC were identified using immunohistochemistry and immunofluorescence.Results: Three distinct m6A modification clusters were identified. The m6A clusters were significantly associated with clinical features, prognosis, and immune cell infiltration. The three clusters were highly consistent with the three tumor immune phenotypes, i.e., immune-excluded, immune-inflamed, and immune-desert. Comprehensive bioinformatics analysis revealed that high m6Ascore was closely associated with tumor progression, poor prognosis, and immunotherapy non-response. m6A regulators were dysregulated in HCC tissues. Hence, they play a role as predictors of poor prognosis. Tissue microarray demonstrated that overexpressed YTHDF1 was associated with low CD3+ and CD8+ T cell infiltration in HCC.Conclusion: Our findings demonstrate that m6A modification patterns play a crucial role in the tumor immune microenvironment and the prognosis of HCC. High YTHDF1 expression is closely associated with low CD3+ and CD8+ T cell infiltration in HCC.

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

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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