Identification of a glutamine metabolism reprogramming signature for predicting prognosis, immunotherapy efficacy, and drug candidates in bladder cancer
BackgroundBladder cancer is the most common malignancy of the urinary system. However, patient prognosis and treatment outcomes in bladder cancer are difficult to predict owing to high tumor heterogeneity. Given that abnormal glutamine metabolism has been identified as a key factor driving the progr...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1111319/full |
| _version_ | 1797897074113511424 |
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| author | Yan Xu Zhixiu Xia Xiaoyu Sun Baojun Wei Yang Fu Du Shi Yuyan Zhu |
| author_facet | Yan Xu Zhixiu Xia Xiaoyu Sun Baojun Wei Yang Fu Du Shi Yuyan Zhu |
| author_sort | Yan Xu |
| collection | DOAJ |
| description | BackgroundBladder cancer is the most common malignancy of the urinary system. However, patient prognosis and treatment outcomes in bladder cancer are difficult to predict owing to high tumor heterogeneity. Given that abnormal glutamine metabolism has been identified as a key factor driving the progression of bladder cancer, it is necessary to assess the prognosis and therapeutic efficacy of bladder cancer treatments based on an analysis of glutamine metabolism-related genes.MethodsWe used bladder cancer sample data downloaded from The Cancer Genome Atlas to identify glutamine metabolism-related genes as prognostic markers, and established a novel Glutamine Metabolism Immunity Index (GMII) based on univariate and multivariate COX regression analyses. On the basis of GMII values, bladder cancer patients were divided into high- and low-risk groups, and systematic analysis was conducted for clinical features, somatic mutations, immune cell infiltration, chemotherapeutic response, and immunotherapeutic efficacy. Candidate small-molecule drugs targeting the GMII core target proteins were identified based on molecular docking analysis.ResultsThe GMII consisting of eight independent prognostic genes was established to be an excellent tool for predicting the survival in patients with bladder cancer and was validated using multiple datasets. Compared with patients in the high-risk group, those in the low-risk group had significantly better responses to gemcitabine and immune checkpoint blockade. In addition, we predicted 12 potential small-molecule drugs that could bind to three of the GMII core target proteins.ConclusionsThe GMII can be used to accurately predict the prognosis and immunotherapeutic response of bladder cancer patients, as well as candidate small-molecule drugs. Furthermore, the novel “Glutamine Metabolism-related Gene”-guided strategy for predicting survival and chemo-immunotherapeutic efficacy may also be applicable for cancers other than bladder cancer. |
| first_indexed | 2024-04-10T07:51:54Z |
| format | Article |
| id | doaj.art-4eb8e0c75f2f481d9be4c995f17dcc74 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T07:51:54Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4eb8e0c75f2f481d9be4c995f17dcc742023-02-23T09:21:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-02-011410.3389/fimmu.2023.11113191111319Identification of a glutamine metabolism reprogramming signature for predicting prognosis, immunotherapy efficacy, and drug candidates in bladder cancerYan Xu0Zhixiu Xia1Xiaoyu Sun2Baojun Wei3Yang Fu4Du Shi5Yuyan Zhu6Department of Urology, The First Hospital of China Medical University, Shenyang, ChinaColorectal Tumor Surgery Ward, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Pharmacology, School of Pharmacy, China Medical University, Shenyang, ChinaDepartment of Urology, The First Hospital of China Medical University, Shenyang, ChinaDepartment of Urology, The First Hospital of China Medical University, Shenyang, ChinaDepartment of Urology, The First Hospital of China Medical University, Shenyang, ChinaDepartment of Urology, The First Hospital of China Medical University, Shenyang, ChinaBackgroundBladder cancer is the most common malignancy of the urinary system. However, patient prognosis and treatment outcomes in bladder cancer are difficult to predict owing to high tumor heterogeneity. Given that abnormal glutamine metabolism has been identified as a key factor driving the progression of bladder cancer, it is necessary to assess the prognosis and therapeutic efficacy of bladder cancer treatments based on an analysis of glutamine metabolism-related genes.MethodsWe used bladder cancer sample data downloaded from The Cancer Genome Atlas to identify glutamine metabolism-related genes as prognostic markers, and established a novel Glutamine Metabolism Immunity Index (GMII) based on univariate and multivariate COX regression analyses. On the basis of GMII values, bladder cancer patients were divided into high- and low-risk groups, and systematic analysis was conducted for clinical features, somatic mutations, immune cell infiltration, chemotherapeutic response, and immunotherapeutic efficacy. Candidate small-molecule drugs targeting the GMII core target proteins were identified based on molecular docking analysis.ResultsThe GMII consisting of eight independent prognostic genes was established to be an excellent tool for predicting the survival in patients with bladder cancer and was validated using multiple datasets. Compared with patients in the high-risk group, those in the low-risk group had significantly better responses to gemcitabine and immune checkpoint blockade. In addition, we predicted 12 potential small-molecule drugs that could bind to three of the GMII core target proteins.ConclusionsThe GMII can be used to accurately predict the prognosis and immunotherapeutic response of bladder cancer patients, as well as candidate small-molecule drugs. Furthermore, the novel “Glutamine Metabolism-related Gene”-guided strategy for predicting survival and chemo-immunotherapeutic efficacy may also be applicable for cancers other than bladder cancer.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1111319/fullbladder cancerglutamine metabolismimmunotherapy efficacyprognosismolecular docking |
| spellingShingle | Yan Xu Zhixiu Xia Xiaoyu Sun Baojun Wei Yang Fu Du Shi Yuyan Zhu Identification of a glutamine metabolism reprogramming signature for predicting prognosis, immunotherapy efficacy, and drug candidates in bladder cancer Frontiers in Immunology bladder cancer glutamine metabolism immunotherapy efficacy prognosis molecular docking |
| title | Identification of a glutamine metabolism reprogramming signature for predicting prognosis, immunotherapy efficacy, and drug candidates in bladder cancer |
| title_full | Identification of a glutamine metabolism reprogramming signature for predicting prognosis, immunotherapy efficacy, and drug candidates in bladder cancer |
| title_fullStr | Identification of a glutamine metabolism reprogramming signature for predicting prognosis, immunotherapy efficacy, and drug candidates in bladder cancer |
| title_full_unstemmed | Identification of a glutamine metabolism reprogramming signature for predicting prognosis, immunotherapy efficacy, and drug candidates in bladder cancer |
| title_short | Identification of a glutamine metabolism reprogramming signature for predicting prognosis, immunotherapy efficacy, and drug candidates in bladder cancer |
| title_sort | identification of a glutamine metabolism reprogramming signature for predicting prognosis immunotherapy efficacy and drug candidates in bladder cancer |
| topic | bladder cancer glutamine metabolism immunotherapy efficacy prognosis molecular docking |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1111319/full |
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