Comprehensive Analysis of the Butyrate-Metabolism-Related Gene Signature in Tumor Microenvironment-Infiltrating Immune Cells in Clear Cell Renal Cell Carcinoma
A wealth of experimental evidence has validated that butyrate is capable of inhibiting tumorigenesis, while the potential role of butyrate metabolism in the tumor immune microenvironment (TIME) has been rarely explored. This study aims to explore the potential of butyrate-metabolism-related genes as...
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.816024/full |
| _version_ | 1828348320169328640 |
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| author | Gang Tang Haochen Guan Zhiyong Du Weijie Yuan |
| author_facet | Gang Tang Haochen Guan Zhiyong Du Weijie Yuan |
| author_sort | Gang Tang |
| collection | DOAJ |
| description | A wealth of experimental evidence has validated that butyrate is capable of inhibiting tumorigenesis, while the potential role of butyrate metabolism in the tumor immune microenvironment (TIME) has been rarely explored. This study aims to explore the potential of butyrate-metabolism-related genes as prognostic biomarkers and their correlations with immune infiltrates in clear cell renal cell carcinoma (ccRCC) patients. Based on The Cancer Genome Atlas dataset (TCGA; n = 539), a total of 22 differentially expressed genes (DEGs) related with butyrate metabolism in ccRCC and normal samples were identified. Among them, a prognostic signature involving six butyrate-metabolism-related genes was created (Bu-Meta-GPS) in the training set (n = 271) and validation set (n = 268), and risk scores were calculated based on them. ccRCC patients with high-risk scores exhibited an unfavorable prognosis, high immunoscore, upregulated immuno-oncological targets (PD1, PD-L1, CTLA4, and CD19), and distinct immune-cell infiltration than those with low-risk scores. High-risk ccRCC patients without radiotherapy had a better survival rate than radiotherapy-treated patients. The negative regulation of cytokine production and cytokine-mediated signaling pathways was remarkably enriched in ccRCC patients with high-risk scores. A nomogram was then formulated to assess the overall survival (OS) of ccRCC patients. In summary, we illuminated the key role of butyrate metabolism in ccRCC TIME. The developed Bu-Meta-GPS was a sensitive predictive biomarker for the prognosis of ccRCC, which also provided new perspectives in improving immunotherapeutic efficacy. |
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| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-14T00:53:11Z |
| publishDate | 2022-05-01 |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-fb33c9740c754f02a84959f3b9a8c1462022-12-22T02:21:44ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-05-011010.3389/fcell.2022.816024816024Comprehensive Analysis of the Butyrate-Metabolism-Related Gene Signature in Tumor Microenvironment-Infiltrating Immune Cells in Clear Cell Renal Cell CarcinomaGang Tang0Haochen Guan1Zhiyong Du2Weijie Yuan3Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Urology Surgery, Dingzhou People’s Hospital of Hebei Province, Dingzhou, ChinaDepartment of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaA wealth of experimental evidence has validated that butyrate is capable of inhibiting tumorigenesis, while the potential role of butyrate metabolism in the tumor immune microenvironment (TIME) has been rarely explored. This study aims to explore the potential of butyrate-metabolism-related genes as prognostic biomarkers and their correlations with immune infiltrates in clear cell renal cell carcinoma (ccRCC) patients. Based on The Cancer Genome Atlas dataset (TCGA; n = 539), a total of 22 differentially expressed genes (DEGs) related with butyrate metabolism in ccRCC and normal samples were identified. Among them, a prognostic signature involving six butyrate-metabolism-related genes was created (Bu-Meta-GPS) in the training set (n = 271) and validation set (n = 268), and risk scores were calculated based on them. ccRCC patients with high-risk scores exhibited an unfavorable prognosis, high immunoscore, upregulated immuno-oncological targets (PD1, PD-L1, CTLA4, and CD19), and distinct immune-cell infiltration than those with low-risk scores. High-risk ccRCC patients without radiotherapy had a better survival rate than radiotherapy-treated patients. The negative regulation of cytokine production and cytokine-mediated signaling pathways was remarkably enriched in ccRCC patients with high-risk scores. A nomogram was then formulated to assess the overall survival (OS) of ccRCC patients. In summary, we illuminated the key role of butyrate metabolism in ccRCC TIME. The developed Bu-Meta-GPS was a sensitive predictive biomarker for the prognosis of ccRCC, which also provided new perspectives in improving immunotherapeutic efficacy.https://www.frontiersin.org/articles/10.3389/fcell.2022.816024/fullbutyratemetabolismtumor immune microenvironmentccRCCgene signature |
| spellingShingle | Gang Tang Haochen Guan Zhiyong Du Weijie Yuan Comprehensive Analysis of the Butyrate-Metabolism-Related Gene Signature in Tumor Microenvironment-Infiltrating Immune Cells in Clear Cell Renal Cell Carcinoma Frontiers in Cell and Developmental Biology butyrate metabolism tumor immune microenvironment ccRCC gene signature |
| title | Comprehensive Analysis of the Butyrate-Metabolism-Related Gene Signature in Tumor Microenvironment-Infiltrating Immune Cells in Clear Cell Renal Cell Carcinoma |
| title_full | Comprehensive Analysis of the Butyrate-Metabolism-Related Gene Signature in Tumor Microenvironment-Infiltrating Immune Cells in Clear Cell Renal Cell Carcinoma |
| title_fullStr | Comprehensive Analysis of the Butyrate-Metabolism-Related Gene Signature in Tumor Microenvironment-Infiltrating Immune Cells in Clear Cell Renal Cell Carcinoma |
| title_full_unstemmed | Comprehensive Analysis of the Butyrate-Metabolism-Related Gene Signature in Tumor Microenvironment-Infiltrating Immune Cells in Clear Cell Renal Cell Carcinoma |
| title_short | Comprehensive Analysis of the Butyrate-Metabolism-Related Gene Signature in Tumor Microenvironment-Infiltrating Immune Cells in Clear Cell Renal Cell Carcinoma |
| title_sort | comprehensive analysis of the butyrate metabolism related gene signature in tumor microenvironment infiltrating immune cells in clear cell renal cell carcinoma |
| topic | butyrate metabolism tumor immune microenvironment ccRCC gene signature |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.816024/full |
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