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Development of a prognostic model of glioma based on immune-related genes.

ABSTRACT: Glioma is the most common type of primary brain cancer, and the prognosis of most patients with glioma, and particularly that of patients with glioblastoma, is poor. Tumor immunity serves an important role in the development of glioma. However, immunotherapy for glioma has not been completely successful, and thus, comprehensive examination of the immune-related genes (IRGs) of glioma is required. In the present study, differentially expressed genes (DEGs) and differentially expressed IRGs (DEIRGs) were identified using the edgeR package. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used for functional enrichment analysis of DEIRGs. Survival-associated IRGs were selected via univariate Cox regression analysis. A The Cancer Genome Atlas prognostic model and GSE43378 validation model were established using lasso-penalized Cox regression analysis. Based on the median risk score value, patients were divided into high-risk and low-risk groups for clinical analysis. Receiver operating characteristic curve and nomogram analyses were used to assess the accuracy of the models. Reverse transcription-quantitative PCR was performed to measure the expression levels of relevant genes, such as cyclin-dependent kinase 4 (CDK4), interleukin 24 (IL24), NADPH oxidase 4 (NOX4), bone morphogenetic protein 2 (BMP2) and baculoviral IAP repeat containing 5 (BIRC5). A total of 3,238 DEGs, including 1,950 upregulated and 1,288 downregulated DEGs, and 97 DEIRGs, including 60 upregulated and 37 downregulated DEIRGs, were identified. 'Neuroactive ligand-receptor interaction' and 'Cytokine-cytokine receptor interaction' were the most significantly enriched pathways according to KEGG pathway analysis. A prognostic model and a validation prognostic model were created for glioma, including 15 survival-associated IRGs (FCER1G, NOX4, TRIM5, SOCS1, APOBEC3C, BIRC5, VIM, TNC, BMP2, CMTM3, IL24, JAG1, CALCRL, HNF4G and CDK4). Furthermore, multivariate Cox regression analysis results suggested that age, high WHO Grade by histopathology, wild type isocitrate dehydrogenase 1 and high risk score were independently associated with poor overall survival. The infiltration of B cells, CD8⁺ T cells, dendritic cells, macrophages and neutrophils was positively associated with the prognostic risk score. In the present study, several clinically significant survival-associated IRGs were identified, and a prognosis evaluation model of glioma was established.

SUBMITTER: Wang JJ

PROVIDER: S-EPMC7751470 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Development of a prognostic model of glioma based on immune-related genes.

Wang Jing-Jing JJ Wang Han H Zhu Bao-Long BL Wang Xiang X Qian Yong-Hong YH Xie Lei L Wang Wen-Jie WJ Zhu Jie J Chen Xing-Yu XY Wang Jing-Mei JM Ding Zhi-Liang ZL

Oncology letters 20201215 2

Glioma is the most common type of primary brain cancer, and the prognosis of most patients with glioma, and particularly that of patients with glioblastoma, is poor. Tumor immunity serves an important role in the development of glioma. However, immunotherapy for glioma has not been completely successful, and thus, comprehensive examination of the immune-related genes (IRGs) of glioma is required. In the present study, differentially expressed genes (DEGs) and differentially expressed IRGs (DEIRG ...[more]

PMID: 33376548

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Project description:BackgroundStudies have shown that Nicotinamide adenine dinucleotide (NAD+) metabolism can promote the occurrence and development of glioma. However, the specific effects and mechanisms of NAD+ metabolism in glioma are unclear and there were no systematic researches about NAD+ metabolism related genes to predict the survival of patients with glioma.MethodsThe research was performed based on expression data of glioma cases in the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Firstly, TCGA-glioma cases were classified into different subtypes based on 49 NAD+ metabolism-related genes (NMRGs) by consensus clustering. NAD+ metabolism-related differentially expressed genes (NMR-DEGs) were gotten by intersecting the 49 NMRGs and differentially expressed genes (DEGs) between normal and glioma samples. Then a risk model was built by Cox analysis and the least shrinkage and selection operator (LASSO) regression analysis. The validity of the model was verified by survival curves and receiver operating characteristic (ROC) curves. In addition, independent prognostic analysis of the risk model was performed by Cox analysis. Then, we also identified different immune cells, HLA family genes and immune checkpoints between high and low risk groups. Finally, the functions of model genes at single-cell level were also explored.ResultsConsensus clustering classified glioma patients into two subtypes, and the overall survival (OS) of the two subtypes differed. A total of 11 NAD+ metabolism-related differentially expressed genes (NMR-DEGs) were screened by overlapping 5,995 differentially expressed genes (DEGs) and 49 NAD+ metabolism-related genes (NMRGs). Next, four model genes, PARP9, BST1, NMNAT2, and CD38, were obtained by Cox regression and least absolute shrinkage and selection operator (Lasso) regression analyses and to construct a risk model. The OS of high-risk group was lower. And the area under curves (AUCs) of Receiver operating characteristic (ROC) curves were >0.7 at 1, 3, and 5 years. Cox analysis showed that age, grade G3, grade G4, IDH status, ATRX status, BCR status, and risk Scores were reliable independent prognostic factors. In addition, three different immune cells, Mast cells activated, NK cells activated and B cells naive, 24 different HLA family genes, such as HLA-DPA1 and HLA-H, and 8 different immune checkpoints, such as ICOS, LAG3, and CD274, were found between the high and low risk groups. The model genes were significantly relevant with proliferation, cell differentiation, and apoptosis.ConclusionThe four genes, PARP9, BST1, NMNAT2, and CD38, might be important molecular biomarkers and therapeutic targets for glioma patients.

Project description:Background: Long non-coding RNAs (lncRNAs) play an important role in the immune processes of glioma. Immune related lncRNAs (IRlncRs) may be a critical prognosis in patients with glioma. The current study aimed to construct a glioma immune-related prognosis model by IRlncRs. Methods: Transcriptome RNA-sequencing data of glioma were obtained from The Cancer Genome Atlas (TCGA) and an immune‑related risk score (IRRS) model was constructed by Lasso and multivariate Cox regression analysis. Receiver Operating Characteristic (ROC) curves were used to assess the sensitivity and specificity of the prognosis on IRRS. A predictive nomogram and a time-dependent ROC curve was performed in training and validation cohort. We explored the relationships between survival‑related IRlncRs (sIRlncRs) and clinicopathologic parameters. Functional annotation of the sIRlncRs was investigated by gene set enrichment analysis (GSEA) and principal component analysis (PCA). The relationships between IRRS model and immune cell infiltration and co-expression network analysis among the sIRlncRs were performed for molecular mechanism study. Results: A total of 10 sIRlncRs were enrolled to build IRRS model. The IRRS was identified as an independent prognostic factor and correlated with the overall survival (AUC =0.880). The nomogram was constructed successfully with IRRS, age and grade as variables. Immune cell infiltration analysis indicated that B cells, neutrophil, dendritic and macrophage cells were positively correlated with IRRS. PCA and GSEA illustrated that the lncRNA signature enrolled the IRRS model was closely related to immune status. Additionally, co-expression network showed that there was a strong correlation between 10 sIRlncRs at the transcriptional level. Conclusion: We successfully constructed a remarkable clinical model of sIRlncRs with potential prognostic value for glioma patients, which provides an insight into immunological research and treatment strategies of glioma.

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Project description:BackgroundBreast cancer is one of the main malignant tumors that threaten the lives of women, which has received more and more clinical attention worldwide. There are increasing evidences showing that the immune micro-environment of breast cancer (BC) seriously affects the clinical outcome. This study aims to explore the role of tumor immune genes in the prognosis of BC patients and construct an immune-related genes prognostic index.MethodsThe list of 2498 immune genes was obtained from ImmPort database. In addition, gene expression data and clinical characteristics data of BC patients were also obtained from the TCGA database. The prognostic correlation of the differential genes was analyzed through Survival package. Cox regression analysis was performed to analyze the prognostic effect of immune genes. According to the regression coefficients of prognostic immune genes in regression analysis, an immune risk scores model was established. Gene set enrichment analysis (GSEA) was performed to probe the biological correlation of immune gene scores. P < 0.05 was considered to be statistically significant.ResultsIn total, 556 immune genes were differentially expressed between normal tissues and BC tissues (p < 0. 05). According to the univariate cox regression analysis, a total of 66 immune genes were statistically significant for survival risk, of which 30 were associated with overall survival (P < 0.05). Finally, a 15 immune genes risk scores model was established. All patients were divided into high- and low-groups. KM survival analysis revealed that high immune risk scores represented worse survival (p < 0.001). ROC curve indicated that the immune genes risk scores model had a good reliability in predicting prognosis (5-year OS, AUC = 0.752). The established risk model showed splendid AUC value in the validation dataset (3-year over survival (OS) AUC = 0.685, 5-year OS AUC = 0.717, P = 0.00048). Moreover, the immune risk signature was proved to be an independent prognostic factor for BC patients. Finally, it was found that 15 immune genes and risk scores had significant clinical correlations, and were involved in a variety of carcinogenic pathways.ConclusionIn conclusion, our study provides a new perspective for the expression of immune genes in BC. The constructed model has potential value for the prognostic prediction of BC patients and may provide some references for the clinical precision immunotherapy of patients.

Project description:BackgroundThe importance of pyroptosis in tumorigenesis and cancer progression is becoming increasingly apparent. However, the efficacy of using pyroptosis-related genes (PRGs) in predicting the prognosis of pancreatic adenocarcinoma (PAAD) patients is unknown.MethodsThis investigation used two databases to obtain expression data for PAAD patients. Differentially expressed PRGs (DEPRGs) were identified between PAAD and control samples. Several bioinformatic approaches were used to analyze the biological functions of DEPRGs and to identify prognostic DERPGs. A miRNA-prognostic DEPRG-transcription factor (TF) regulatory network was created via the miRNet online tool. A risk score model was created after each patient's risk score was calculated. The microenvironments of the low- and high-risk groups were assessed using xCell, the expression of immune checkpoints was determined, and gene set variation analysis (GSVA) was performed. Finally, the efficacy of certain potential drugs was predicted using the pRRophetic algorithm, and the results in the high- and low-risk groups were compared.ResultsA total of 13 DEPRGs were identified between PAAD and control samples. Functional enrichment analysis showed that the DEPRGs had a close relationship with inflammation. In univariate and multivariate Cox regression analyses, GSDMC, IRF1, and PLCG1 were identified as prognostic biomarkers in PAAD. The results of the miRNA-prognostic DEPRG-TF regulatory network showed that GSDMC, IRF1, and PLCG1 were regulated by both specific and common miRNAs and TFs. Based on the risk score and other independent prognostic indicators, a nomogram with a good ability to predict the survival of PAAD patients was developed. By evaluating the tumor microenvironment, we observed that the immune and metabolic microenvironments of the two groups were substantially different. In addition, individuals in the low-risk group were more susceptible to axitinib and camptothecin, whereas lapatinib might be preferred for patients in the high-risk group.ConclusionOur study revealed the prognostic value of PRGs in PAAD and created a reliable model for predicting the prognosis of PAAD patients. Our findings will benefit the prognostication and treatment of PAAD patients.

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Development of a prognostic model of glioma based on immune-related genes.

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Development of a prognostic model of glioma based on immune-related genes.

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