Deciphering a Novel Necroptosis-Related miRNA Signature for Predicting the Prognosis of Clear Cell Renal Carcinoma
Clear cell renal cell carcinoma (ccRCC) is the most common histological and devastating subtype of renal cell carcinoma. Necroptosis is a form of programmed cell death that causes prominent inflammatory responses. miRNAs play a significant role in cancer progression through necroptosis. However, the...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Analytical Cellular Pathology |
| Online Access: | http://dx.doi.org/10.1155/2022/2721005 |
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| author | Jia-hao Bao Jiang-bo Li Han-sen Lin Wen-jin Zhang Bing-yan Guo Jun-jie Li Liang-min Fu Yang-peng Sun |
| author_facet | Jia-hao Bao Jiang-bo Li Han-sen Lin Wen-jin Zhang Bing-yan Guo Jun-jie Li Liang-min Fu Yang-peng Sun |
| author_sort | Jia-hao Bao |
| collection | DOAJ |
| description | Clear cell renal cell carcinoma (ccRCC) is the most common histological and devastating subtype of renal cell carcinoma. Necroptosis is a form of programmed cell death that causes prominent inflammatory responses. miRNAs play a significant role in cancer progression through necroptosis. However, the prognostic value of necroptosis-related miRNAs remains ambiguous. In this study, 39 necroptosis-related miRNAs (NRMs) were extracted and 17 differentially expressed NRMs between normal and tumor samples were identified using data form The Cancer Genome Atlas (TCGA). After applying univariate Cox proportional hazard regression analysis and LASSO Cox regression model, six necroptosis-related miRNA signatures were identified in the training cohort and their expression levels were verified by qRT-PCR. Using the expression levels of these miRNAs, all patients were divided into the high- and low-risk groups. Patients in the high-risk group showed poor overall survival (P<0.0001). Time-dependent ROC curves confirmed the good performance of our signature. The results were verified in the testing cohort and the entire TCGA cohort. Univariate and multivariate Cox regression models demonstrated that the risk score was an independent prognostic factor. Additionally, a predictive nomogram with good performance was constructed to enhance the implementation of the constructed signature in a clinical setting. We then employed miRBD, miRTarBase, and TargetScan to predict the target genes of six necroptosis-related miRNAs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that 392 potential target genes were enriched in cell proliferation-related biological processes. Six miRNAs and 59 differentially expressed target genes were used to construct an miRNA–mRNA interaction network, and 11 hub genes were selected for survival and tumor infiltration analysis. Drug sensitivity analysis revealed potential drugs that may contribute to cancer management. Hence, necroptosis-related genes play an important role in cancer biology. We developed, for the first time, a necroptosis-related miRNA signature to predict ccRCC prognosis. |
| format | Article |
| id | doaj-art-9cfb1edfe23340188f8e121b645311f2 |
| institution | Kabale University |
| issn | 2210-7185 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Analytical Cellular Pathology |
| spelling | doaj-art-9cfb1edfe23340188f8e121b645311f22025-08-20T03:38:15ZengWileyAnalytical Cellular Pathology2210-71852022-01-01202210.1155/2022/2721005Deciphering a Novel Necroptosis-Related miRNA Signature for Predicting the Prognosis of Clear Cell Renal CarcinomaJia-hao Bao0Jiang-bo Li1Han-sen Lin2Wen-jin Zhang3Bing-yan Guo4Jun-jie Li5Liang-min Fu6Yang-peng Sun7Hospital of StomatologyHospital of StomatologyDepartment of UrologyHospital of StomatologyHospital of StomatologyHospital of StomatologyDepartment of UrologyHospital of StomatologyClear cell renal cell carcinoma (ccRCC) is the most common histological and devastating subtype of renal cell carcinoma. Necroptosis is a form of programmed cell death that causes prominent inflammatory responses. miRNAs play a significant role in cancer progression through necroptosis. However, the prognostic value of necroptosis-related miRNAs remains ambiguous. In this study, 39 necroptosis-related miRNAs (NRMs) were extracted and 17 differentially expressed NRMs between normal and tumor samples were identified using data form The Cancer Genome Atlas (TCGA). After applying univariate Cox proportional hazard regression analysis and LASSO Cox regression model, six necroptosis-related miRNA signatures were identified in the training cohort and their expression levels were verified by qRT-PCR. Using the expression levels of these miRNAs, all patients were divided into the high- and low-risk groups. Patients in the high-risk group showed poor overall survival (P<0.0001). Time-dependent ROC curves confirmed the good performance of our signature. The results were verified in the testing cohort and the entire TCGA cohort. Univariate and multivariate Cox regression models demonstrated that the risk score was an independent prognostic factor. Additionally, a predictive nomogram with good performance was constructed to enhance the implementation of the constructed signature in a clinical setting. We then employed miRBD, miRTarBase, and TargetScan to predict the target genes of six necroptosis-related miRNAs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that 392 potential target genes were enriched in cell proliferation-related biological processes. Six miRNAs and 59 differentially expressed target genes were used to construct an miRNA–mRNA interaction network, and 11 hub genes were selected for survival and tumor infiltration analysis. Drug sensitivity analysis revealed potential drugs that may contribute to cancer management. Hence, necroptosis-related genes play an important role in cancer biology. We developed, for the first time, a necroptosis-related miRNA signature to predict ccRCC prognosis.http://dx.doi.org/10.1155/2022/2721005 |
| spellingShingle | Jia-hao Bao Jiang-bo Li Han-sen Lin Wen-jin Zhang Bing-yan Guo Jun-jie Li Liang-min Fu Yang-peng Sun Deciphering a Novel Necroptosis-Related miRNA Signature for Predicting the Prognosis of Clear Cell Renal Carcinoma Analytical Cellular Pathology |
| title | Deciphering a Novel Necroptosis-Related miRNA Signature for Predicting the Prognosis of Clear Cell Renal Carcinoma |
| title_full | Deciphering a Novel Necroptosis-Related miRNA Signature for Predicting the Prognosis of Clear Cell Renal Carcinoma |
| title_fullStr | Deciphering a Novel Necroptosis-Related miRNA Signature for Predicting the Prognosis of Clear Cell Renal Carcinoma |
| title_full_unstemmed | Deciphering a Novel Necroptosis-Related miRNA Signature for Predicting the Prognosis of Clear Cell Renal Carcinoma |
| title_short | Deciphering a Novel Necroptosis-Related miRNA Signature for Predicting the Prognosis of Clear Cell Renal Carcinoma |
| title_sort | deciphering a novel necroptosis related mirna signature for predicting the prognosis of clear cell renal carcinoma |
| url | http://dx.doi.org/10.1155/2022/2721005 |
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