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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...

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Autores principales: Cai, Manbo, Yang, Qiao, He, Junyan, Wu, Haibiao, Li, Zhimin, Fang, Zhe, Li, Jianjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10005877/
https://www.ncbi.nlm.nih.gov/pubmed/36910333
http://dx.doi.org/10.1155/2023/8446765
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author Cai, Manbo
Yang, Qiao
He, Junyan
Wu, Haibiao
Li, Zhimin
Fang, Zhe
Li, Jianjun
author_facet Cai, Manbo
Yang, Qiao
He, Junyan
Wu, Haibiao
Li, Zhimin
Fang, Zhe
Li, Jianjun
author_sort Cai, Manbo
collection PubMed
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.
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spelling pubmed-100058772023-03-11 Identification and Validation of a Necroptosis-Related Prognostic Signature for Kidney Renal Clear Cell Carcinoma Cai, Manbo Yang, Qiao He, Junyan Wu, Haibiao Li, Zhimin Fang, Zhe Li, Jianjun Stem Cells Int Research Article 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. Hindawi 2023-03-03 /pmc/articles/PMC10005877/ /pubmed/36910333 http://dx.doi.org/10.1155/2023/8446765 Text en Copyright © 2023 Manbo Cai et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Cai, Manbo
Yang, Qiao
He, Junyan
Wu, Haibiao
Li, Zhimin
Fang, Zhe
Li, Jianjun
Identification and Validation of a Necroptosis-Related Prognostic Signature for Kidney Renal Clear Cell Carcinoma
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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10005877/
https://www.ncbi.nlm.nih.gov/pubmed/36910333
http://dx.doi.org/10.1155/2023/8446765
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