Identification and Validation of a Necroptosis-Related Prognostic Signature for Kidney Renal Clear Cell Carcinoma
Background. Necroptosis is progressively becoming an important focus of research because of its role in the pathogenesis of cancer and other inflammatory diseases. Our study is designed to anticipate the survival time of kidney renal clear cell carcinoma (KIRC) by constructing a prognostic signature...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Hindawi Limited
2023-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2023/8446765 |
| _version_ | 1811154783312019456 |
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| author | Manbo Cai Qiao Yang Junyan He Haibiao Wu Zhimin Li Zhe Fang Jianjun Li |
| author_facet | Manbo Cai Qiao Yang Junyan He Haibiao Wu Zhimin Li Zhe Fang Jianjun Li |
| author_sort | Manbo Cai |
| collection | DOAJ |
| description | Background. Necroptosis is progressively becoming an important focus of research because of its role in the pathogenesis of cancer and other inflammatory diseases. Our study is designed to anticipate the survival time of kidney renal clear cell carcinoma (KIRC) by constructing a prognostic signature of necroptosis-related genes. Materials. Clinical information and RNA-seq data were acquired from Renal Cell Cancer-European Union (RECA-EU) and The Cancer Genome Atlas- (TCGA-) KIRC, respectively. ConsensusClusterPlus was used to identify molecular subtypes, and the distribution of immune cell infiltration, anticancer drug sensitivity, and somatic gene mutations was studied in these subtypes. Subsequently, LASSO-Cox regression and univariate Cox regression were also carried out to construct a necroptosis-related signature. Cox regression, survival analysis, clinicopathological characteristic correlation analysis, nomogram, cancer stem cell analysis, and receiver operating characteristic (ROC) curve were some tools employed to study the prognostic power of the signature. Results. Based on the expression patterns of 66 survival-related necroptosis genes, we classified the KIRC into three subtypes (C1, C2, and C3) that are associated with necroptosis, which had significantly different tumor stem cell components. Among these, C2 patients had a longer survival time and enhanced immune status and were more sensitive to conventional chemotherapeutic drugs. Moreover, in order to predict the prognosis of KIRC patients, five genes (BMP8A, TLCD1, CLGN, GDF7, and RARB) were used to develop a necroptosis-related prognostic signature, which had an acceptable predictive potency. The results from Cox regression and stratified survival analysis revealed that the signature was an independent prognostic factor, whereas the nomogram and calibration curve demonstrated satisfactory survival time prediction based on the risk score. Conclusions. Three molecular subtypes and five necroptosis-related genes were discovered in KIRC using data from TCGA-KIRC and RECA-EU. Thus, a new biomarker and a potentially effective therapeutic approach for KIRC patients were provided in the current study. |
| first_indexed | 2024-04-10T04:22:52Z |
| format | Article |
| id | doaj.art-773ef7f2a51d4507a0e826d5a5124239 |
| institution | Directory Open Access Journal |
| issn | 1687-9678 |
| language | English |
| last_indexed | 2024-04-10T04:22:52Z |
| publishDate | 2023-01-01 |
| publisher | Hindawi Limited |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj.art-773ef7f2a51d4507a0e826d5a51242392023-03-11T00:00:12ZengHindawi LimitedStem Cells International1687-96782023-01-01202310.1155/2023/8446765Identification and Validation of a Necroptosis-Related Prognostic Signature for Kidney Renal Clear Cell CarcinomaManbo Cai0Qiao Yang1Junyan He2Haibiao Wu3Zhimin Li4Zhe Fang5Jianjun Li6Department of Oncology RadiotherapyDepartment of Oncology RadiotherapyDepartment of Oncology RadiotherapyDepartment of Oncology RadiotherapyDepartment of Oncology RadiotherapyDepartment of Oncology RadiotherapyDepartment of Urological SurgicalBackground. Necroptosis is progressively becoming an important focus of research because of its role in the pathogenesis of cancer and other inflammatory diseases. Our study is designed to anticipate the survival time of kidney renal clear cell carcinoma (KIRC) by constructing a prognostic signature of necroptosis-related genes. Materials. Clinical information and RNA-seq data were acquired from Renal Cell Cancer-European Union (RECA-EU) and The Cancer Genome Atlas- (TCGA-) KIRC, respectively. ConsensusClusterPlus was used to identify molecular subtypes, and the distribution of immune cell infiltration, anticancer drug sensitivity, and somatic gene mutations was studied in these subtypes. Subsequently, LASSO-Cox regression and univariate Cox regression were also carried out to construct a necroptosis-related signature. Cox regression, survival analysis, clinicopathological characteristic correlation analysis, nomogram, cancer stem cell analysis, and receiver operating characteristic (ROC) curve were some tools employed to study the prognostic power of the signature. Results. Based on the expression patterns of 66 survival-related necroptosis genes, we classified the KIRC into three subtypes (C1, C2, and C3) that are associated with necroptosis, which had significantly different tumor stem cell components. Among these, C2 patients had a longer survival time and enhanced immune status and were more sensitive to conventional chemotherapeutic drugs. Moreover, in order to predict the prognosis of KIRC patients, five genes (BMP8A, TLCD1, CLGN, GDF7, and RARB) were used to develop a necroptosis-related prognostic signature, which had an acceptable predictive potency. The results from Cox regression and stratified survival analysis revealed that the signature was an independent prognostic factor, whereas the nomogram and calibration curve demonstrated satisfactory survival time prediction based on the risk score. Conclusions. Three molecular subtypes and five necroptosis-related genes were discovered in KIRC using data from TCGA-KIRC and RECA-EU. Thus, a new biomarker and a potentially effective therapeutic approach for KIRC patients were provided in the current study.http://dx.doi.org/10.1155/2023/8446765 |
| spellingShingle | Manbo Cai Qiao Yang Junyan He Haibiao Wu Zhimin Li Zhe Fang Jianjun Li Identification and Validation of a Necroptosis-Related Prognostic Signature for Kidney Renal Clear Cell Carcinoma Stem Cells International |
| title | Identification and Validation of a Necroptosis-Related Prognostic Signature for Kidney Renal Clear Cell Carcinoma |
| title_full | Identification and Validation of a Necroptosis-Related Prognostic Signature for Kidney Renal Clear Cell Carcinoma |
| title_fullStr | Identification and Validation of a Necroptosis-Related Prognostic Signature for Kidney Renal Clear Cell Carcinoma |
| title_full_unstemmed | Identification and Validation of a Necroptosis-Related Prognostic Signature for Kidney Renal Clear Cell Carcinoma |
| title_short | Identification and Validation of a Necroptosis-Related Prognostic Signature for Kidney Renal Clear Cell Carcinoma |
| title_sort | identification and validation of a necroptosis related prognostic signature for kidney renal clear cell carcinoma |
| url | http://dx.doi.org/10.1155/2023/8446765 |
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