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  • Frontiers Media SA  (6)
  • Liu, Yanhui  (6)
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  • Frontiers Media SA  (6)
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  • 1
    Online Resource
    Online Resource
    Image4.TIF
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-11-1)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-11-1)
    Abstract: Glioma is the most common malignant tumor in the central nervous system with no significant therapeutic breakthrough in recent years. Most attempts to apply immunotherapy in glioma have failed. Tryptophan and its metabolism can regulate malignant features of cancers and reshape immune microenvironment of tumors. However, the role of tryptophan metabolism in glioma remains unclear. In current study, we explored the relationships between the expression pattern of tryptophan metabolism-related genes (TrMGs) and tumor characteristics, including prognosis and tumor microenvironment of gliomas through analyzing 1,523 patients’ samples from multiple public databases and our own cohort. Based on expression of TrMGs, K-means clustering analysis stratified all glioma patients into two clusters with significantly different TrMG expression patterns, clinicopathological features and immune microenvironment. Furthermore, we constructed a tryptophan metabolism-related genes signature (TrMRS) based on seven essential TrMGs to classify the patients into TrMRS low- and high-risk groups and validated the prognostic value of the TrMRS in multiple cohorts. Higher TrMRS represented for potentially more active tryptophan catabolism, which could subsequently lead to less tryptophan in tumor. The TrMRS high-risk group presented with shorter overall survival, and further analysis confirmed TrMRS as an independent prognostic factor in gliomas. The nomograms uniting TrMRS with other prognostic factors manifested with satisfactory efficacy in predicting the prognosis of glioma patients. Additionally, analyses of tumor immune landscapes demonstrated that higher TrMRS was correlated with more immune cell infiltration and “hot” immunological phenotype. TrMRS was also demonstrated to be positively correlated with the expression of multiple immunotherapy targets, including PD1 and PD-L1. Finally, the TrMRS high-risk group manifested better predicted response to immune checkpoint inhibitors. In conclusion, our study illustrated the relationships between expression pattern of TrMGs and characteristics of gliomas, and presented a novel model based on TrMRS for prognosis prediction in glioma patients. The association between TrMRS and tumor immune microenvironment of gliomas indicated an important role of tryptophan and its metabolism in reshaping immune landscape and the potential ability to guide the application of immunotherapy for gliomas.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2022.1061597
    DOI: 10.3389/fphar.2022.1061597.s001
    DOI: 10.3389/fphar.2022.1061597.s002
    DOI: 10.3389/fphar.2022.1061597.s003
    DOI: 10.3389/fphar.2022.1061597.s004
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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    Online Resource
  • 2
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    A novel score system based on arginine metabolism-related genes to predict prognosis, characterize immune microenvironment, and forecast response to immunotherapy in IDH-wildtype glioblastoma
    Frontiers Media SA ; 2023
    In:  Frontiers in Pharmacology Vol. 14 ( 2023-4-5)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 14 ( 2023-4-5)
    Abstract: Introduction: Glioblastoma is one of the most lethal cancers and leads to more than 200,000 deaths annually. However, despite lots of researchers devoted to exploring novel treatment regime, most of these attempts eventually failed to improve the overall survival of glioblastoma patients in near 20 years. Immunotherapy is an emerging therapy for cancers and have succeeded in many cancers. But most of its application in glioblastoma have been proved with no improvement in overall survival, which may result from the unique immune microenvironment of glioblastoma. Arginine is amino acid and is involved in many physiological processes. Many studies have suggested that arginine and its metabolism can regulate malignancy of multiple cancers and influence the formation of tumor immune microenvironment. However, there is hardly study focusing on the role of arginine metabolism in glioblastoma. Methods: In this research, based on mRNA sequencing data of 560 IDH-wildtype glioblastoma patients from three public cohorts and one our own cohort, we aimed to construct an arginine metabolism-related genes signature (ArMRS) based on four essential arginine metabolism-related genes (ArMGs) that we filtered from all genes with potential relation with arginine metabolism. Subsequently, the glioblastoma patients were classified into ArMRS high-risk and low-risk groups according to calculated optimal cut-off values of ArMRS in these four cohorts. Results: Further validation demonstrated that the ArMRS was an independent prognostic factor and displayed fine efficacy in prediction of glioblastoma patients’ prognosis. Moreover, analyses of tumor immune microenvironment revealed that higher ArMRS was correlated with more immune infiltration and relatively “hot” immunological phenotype. We also demonstrated that ArMRS was positively correlated with the expression of multiple immunotherapy targets, including PD1 and B7-H3. Additionally, the glioblastomas in the ArMRS high-risk group would present with more cytotoxic T cells (CTLs) infiltration and better predicted response to immune checkpoint inhibitors (ICIs). Discussion: In conclusion, our study constructed a novel score system based on arginine metabolism, ArMRS, which presented with good efficacy in prognosis prediction and strong potential to predict unique immunological features, resistance to immunotherapy, and guide the application of immunotherapy in IDH-wild type glioblastoma.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2023.1145828
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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    Online Resource
  • 3
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    Image_5.TIF
    Frontiers Media SA ; 2023
    In:  Frontiers in Neurology Vol. 14 ( 2023-3-10)
    Details
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 14 ( 2023-3-10)
    Abstract: Diffuse gliomas possess a kind of malignant brain tumor with high mortality. Glutamine represents the most abundant and versatile amino acid in the body. Glutamine not only plays an important role in cell metabolism but also involves in cell survival and malignancies progression. Recent studies indicate that glutamine could also affect the metabolism of immune cells in the tumor microenvironment (TME). Materials and methods The transcriptome data and clinicopathological information of patients with glioma were acquired from TCGA, CGGA, and West China Hospital (WCH). The glutamine metabolism-related genes (GMRGs) were retrieved from the Molecular Signature Database. Consensus clustering analysis was used to discover expression patterns of GMRGs, and glutamine metabolism risk scores (GMRSs) were established to model tumor aggressiveness-related GMRG expression signature. ESTIMATE and CIBERSORTx were applied to depict the TME immune landscape. The tumor immunological phenotype analysis and TIDE were utilized for predicting the therapeutic response of immunotherapy. Results A total of 106 GMRGs were retrieved. Two distinct clusters were established by consensus clustering analysis, which showed a close association with the IDH mutational status of gliomas. In both IDH-mutant and IDH-wildtype gliomas, cluster 2 had significantly shorter overall survival compared with cluster 1, and the differentially expressed genes between the two clusters enriched in pathways related to malignant transformation as well as immunity. In silico TME analysis of the two IDH subtypes revealed not only significantly different immune cell infiltrations and immune phenotypes between the GMRG expression clusters but also different predicted responses to immunotherapy. After the screening, a total of 10 GMRGs were selected to build the GMRS. Survival analysis demonstrated the independent prognostic role of GMRS. Prognostic nomograms were established to predict 1-, 2-, and 3-year survival rates in the four cohorts. Conclusion Different subtypes of glutamine metabolism could affect the aggressiveness and TME immune features of diffuse glioma, despite their IDH mutational status. The expression signature of GMRGs could not only predict the outcome of patients with glioma but also be combined into an accurate prognostic nomogram.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fneur.2023.1104738
    DOI: 10.3389/fneur.2023.1104738.s001
    DOI: 10.3389/fneur.2023.1104738.s002
    DOI: 10.3389/fneur.2023.1104738.s003
    DOI: 10.3389/fneur.2023.1104738.s004
    DOI: 10.3389/fneur.2023.1104738.s005
    DOI: 10.3389/fneur.2023.1104738.s006
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2564214-5
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  • 4
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    Table_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-9-20)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-9-20)
    Abstract: Glioma is one of the most malignant intracerebral tumors, whose treatment means was limited, and prognosis was unsatisfactory. Lactate metabolism patterns have been shown to be highly heterogenous among different tumors and produce diverse impact on the tumor microenvironment. To understand the characteristics and implications of lactate metabolism gene expression, we developed a lactate metabolism-related gene expression signature of gliomas based on RNA-sequencing data of a total of 965 patient samples from TCGA, CGGA, and our own glioma cohort. Sixty-three lactate metabolism-related genes (LMGs) were differentially expressed between glioma and normal brain tissue, and consensus clustering analysis identified two clusters distinct LMG expression patterns. The consensus clusters differed in prognosis, molecular characteristics and estimated immune microenvironment landscape involving immune checkpoint proteins, T cell dysfunction and exclusion, as well as tumor purity. Univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) Cox hazard regression was applied in determining of prognosis-related lactate metabolism genes (PRLMGs), on which prognostic lactate metabolism risk score (PLMRS) was constructed. The high PLMRS group was associated with significantly poorer patient outcome. A nomogram containing PLMRS and other independent prognostic variables was established with remarkable predictive performance on patient survival. Exploration on the somatic mutations and copy number variations of the high- and low-PLMRS groups demonstrated their distinct genetic background. Together, our results indicated that the expression signature of LMG was associated with the prognosis of glioma patients and influenced the activity of immune cells in the tumor microenvironment, which may serve as a potential biomarker for predicting response of gliomas to immunotherapy.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2022.1008219
    DOI: 10.3389/fonc.2022.1008219.s001
    DOI: 10.3389/fonc.2022.1008219.s002
    DOI: 10.3389/fonc.2022.1008219.s003
    DOI: 10.3389/fonc.2022.1008219.s004
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 5
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    Online Resource
    Table4.CSV
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-11-10)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-11-10)
    Abstract: Glioma is the most common malignant tumor in the central nervous system. The impact of metabolism on cancer development and the immune microenvironment landscape has recently gained broad attention. Purines are involved in multiple metabolic pathways. It has been proved that purine metabolism could regulate malignant biological behaviors and response to immune checkpoint inhibitors in multiple cancers. However, the relationship of purine metabolism with clinicopathological features and the immune landscape of glioma remains unclear. In this study, we explored the relationships between the expression of purine metabolism-related genes (PuMGs) and tumor features, including prognosis and microenvironment of glioma, based on analyses of 1,523 tumors from 4 public databases and our cohort. Consensus clustering based on 136 PuMGs classified the glioma patients into two clusters with significantly distinguished prognosis and immune microenvironment landscapes. Increased immune infiltration was associated with more aggressive gliomas. The prognostic Purine Metabolism-Related Genes Risk Signature (PuMRS), based on 11 critical PuMGs, stratified the patients into PuMRS low- and high-risk groups in the training set and was validated by validation sets from multiple cohorts. The high-risk group presented with significantly shorter overall survival, and further survival analysis demonstrated that the PuMRS was an independent prognostic factor in glioma. The nomogram combining PuMRS and other clinicopathological factors showed satisfactory accuracy in predicting glioma patients’ prognosis. Furthermore, analyses of the tumor immune microenvironment suggested that higher PuMRS was correlated with increased immune cell infiltration and gene expression signatures of “hotˮ tumors. Gliomas in the PuMRS high-risk group presented a higher expression level of multiple immune checkpoints, including PD-1 and PD-L1, and a better-predicted therapy response to immune checkpoint inhibitors. In conclusion, our study elucidated the relationship between the expression level of PuMGs and the aggressiveness of gliomas. Our study also endorsed the application of PuMRS to construct a new robust model for the prognosis evaluation of glioma patients. The correlations between the profiles of PuMGs expression and tumor immune microenvironment potentially provided guidance for immunotherapy in glioma.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2022.1038272
    DOI: 10.3389/fphar.2022.1038272.s001
    DOI: 10.3389/fphar.2022.1038272.s002
    DOI: 10.3389/fphar.2022.1038272.s003
    DOI: 10.3389/fphar.2022.1038272.s004
    DOI: 10.3389/fphar.2022.1038272.s005
    DOI: 10.3389/fphar.2022.1038272.s006
    DOI: 10.3389/fphar.2022.1038272.s007
    DOI: 10.3389/fphar.2022.1038272.s008
    DOI: 10.3389/fphar.2022.1038272.s009
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
    Location Call Number Limitation Availability
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    Online Resource
  • 6
    Online Resource
    Online Resource
    Table1.DOCX
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-11-17)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-11-17)
    Abstract: Glioma is one of the most lethal cancers and causes more than 200,000 deaths every year. Immunotherapy was an inspiring therapy for multiple cancers but failed in glioma treatment. The importance of serine and glycine and their metabolism has been well-recognized in the physiology of immune cells and microenvironment in multiple cancers. However, their correlation with prognosis, immune cells, and immune microenvironment of glioma remains unclear. In this study, we investigated the relationships between the expression pattern of serine and glycine metabolism-related genes (SGMGs) and clinicopathological features, prognosis, and tumor microenvironment in glioma based on comprehensive analyses of multiple public datasets and our cohort. According to the expression of SGMGs, we conducted the consensus clustering analysis to stratify all patients into four clusters with remarkably distinctive clinicopathological features, prognosis, immune cell infiltration, and immune microenvironment. Subsequently, a serine and glycine metabolism-related genes signature (SGMRS) was constructed based on five critical SGMGs in glioma to stratify patients into SGMRS high- and low-risk groups and tested for its prognostic value. Higher SGMRS expressed genes associated with the synthesis of serine and glycine at higher levels and manifested poorer prognosis. Besides, we confirmed that SGMRS was an independent prognostic factor and constructed nomograms with satisfactory prognosis prediction performance based on SGMRS and other factors. Analyzing the relationship between SGMRS and immune landscape, we found that higher SGMRS correlated with ‘hotter’ immunological phenotype and more immune cell infiltration. Furthermore, the expression levels of multiple immunotherapy-related targets, including PD-1, PD-L1, and B7-H3, were positively correlated with SGMRS, which was validated by the better predicted response to immune checkpoint inhibitors. In conclusion, our study explored the relationships between the expression pattern of SGMGs and tumor features and created novel models to predict the prognosis of glioma patients. The correlation of SGMRS with immune cells and microenvironment in gliomas suggested an essential role of serine and glycine metabolism in reforming immune cells and microenvironment. Finally, the results of our study endorsed the potential application of SGMRS to guide the selection of immunotherapy for gliomas.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2022.1072253
    DOI: 10.3389/fphar.2022.1072253.s001
    DOI: 10.3389/fphar.2022.1072253.s002
    DOI: 10.3389/fphar.2022.1072253.s003
    DOI: 10.3389/fphar.2022.1072253.s004
    DOI: 10.3389/fphar.2022.1072253.s005
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
    Location Call Number Limitation Availability
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    Online Resource
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