A novel necroptosis-related genes signature to predict prognosis and treatment response in bladder cancer

BackgroundNecroptosis, a form of programmed inflammatory cell death, plays a crucial role in tumor development, necrosis, metastasis, and immune response. This study aimed to explore the role of necroptosis in BLCA and construct a new prognostic model to guide clinical treatment and predict individu...

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Main Authors: Dongnuan Yao, Weitao Yu, Xueming Ma, Junqiang Tian
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-11-01
Series:Frontiers in Molecular Biosciences
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Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2024.1493411/full
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author Dongnuan Yao
Dongnuan Yao
Dongnuan Yao
Weitao Yu
Weitao Yu
Weitao Yu
Xueming Ma
Xueming Ma
Xueming Ma
Junqiang Tian
Junqiang Tian
Junqiang Tian
author_facet Dongnuan Yao
Dongnuan Yao
Dongnuan Yao
Weitao Yu
Weitao Yu
Weitao Yu
Xueming Ma
Xueming Ma
Xueming Ma
Junqiang Tian
Junqiang Tian
Junqiang Tian
author_sort Dongnuan Yao
collection DOAJ
description BackgroundNecroptosis, a form of programmed inflammatory cell death, plays a crucial role in tumor development, necrosis, metastasis, and immune response. This study aimed to explore the role of necroptosis in BLCA and construct a new prognostic model to guide clinical treatment and predict individualized treatment response.MethodsThe transcriptome profiling and the corresponding clinical data of BLCA patients were obtained from the Cancer Genome Atlas database (TCGA) and GEO databases. Univariate, multivariate and LASSO Cox regression analyses were used to identify and construct prognostic features associated with necroptosis. We constructed and validated a prognostic model associated with the patient’s overall survival (OS). A nomogram was established to predict the survival rates of BLCA patients. Finally, the correlation between risk scores and tumor immune microenvironment, somatic mutations, immunotherapy, and chemotherapy was comprehensively analyzed.ResultsThe study found two distinct NRG clusters and three gene subtypes, with significant differences in pathway enrichment and immune cell infiltration associated with different NRG clusters in the TME. In addition, we screened out six necroptosis prognosis-related genes (including PPP2R3A; CERCAM; PIK3IP1; CNTN1; CES1 and CD96) to construct a risk score prognostic model. Significant differences in overall survival rate, immune cell infiltration status, and somatic mutations existed between the high and low-risk scores in BLCA patients. Finally, drug sensitivity analysis showed that high-risk patients benefited more from immunotherapy and chemotherapy drugs.ConclusionThis study explores the importance of necroptosis in the prognosis of patients with BLCA, and the prognostic features associated with necroptosis that we identified can serve as new biomarkers to help develop more precise treatment strategies.
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publisher Frontiers Media S.A.
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spelling doaj-art-07a8098ffe6043a198465f4c3a7a7a772024-11-25T05:10:25ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2024-11-011110.3389/fmolb.2024.14934111493411A novel necroptosis-related genes signature to predict prognosis and treatment response in bladder cancerDongnuan Yao0Dongnuan Yao1Dongnuan Yao2Weitao Yu3Weitao Yu4Weitao Yu5Xueming Ma6Xueming Ma7Xueming Ma8Junqiang Tian9Junqiang Tian10Junqiang Tian11Department of Urology, Lanzhou University Second Hospital, Lanzhou, ChinaGansu Province Clinical Research Center for Urinary System Disease, Lanzhou University Second Hospital, Lanzhou, ChinaThe Second Hospital and Clinical Medical School, Lanzhou University, Lanzhou, ChinaDepartment of Urology, Lanzhou University Second Hospital, Lanzhou, ChinaGansu Province Clinical Research Center for Urinary System Disease, Lanzhou University Second Hospital, Lanzhou, ChinaThe Second Hospital and Clinical Medical School, Lanzhou University, Lanzhou, ChinaDepartment of Urology, Lanzhou University Second Hospital, Lanzhou, ChinaGansu Province Clinical Research Center for Urinary System Disease, Lanzhou University Second Hospital, Lanzhou, ChinaThe Second Hospital and Clinical Medical School, Lanzhou University, Lanzhou, ChinaDepartment of Urology, Lanzhou University Second Hospital, Lanzhou, ChinaGansu Province Clinical Research Center for Urinary System Disease, Lanzhou University Second Hospital, Lanzhou, ChinaThe Second Hospital and Clinical Medical School, Lanzhou University, Lanzhou, ChinaBackgroundNecroptosis, a form of programmed inflammatory cell death, plays a crucial role in tumor development, necrosis, metastasis, and immune response. This study aimed to explore the role of necroptosis in BLCA and construct a new prognostic model to guide clinical treatment and predict individualized treatment response.MethodsThe transcriptome profiling and the corresponding clinical data of BLCA patients were obtained from the Cancer Genome Atlas database (TCGA) and GEO databases. Univariate, multivariate and LASSO Cox regression analyses were used to identify and construct prognostic features associated with necroptosis. We constructed and validated a prognostic model associated with the patient’s overall survival (OS). A nomogram was established to predict the survival rates of BLCA patients. Finally, the correlation between risk scores and tumor immune microenvironment, somatic mutations, immunotherapy, and chemotherapy was comprehensively analyzed.ResultsThe study found two distinct NRG clusters and three gene subtypes, with significant differences in pathway enrichment and immune cell infiltration associated with different NRG clusters in the TME. In addition, we screened out six necroptosis prognosis-related genes (including PPP2R3A; CERCAM; PIK3IP1; CNTN1; CES1 and CD96) to construct a risk score prognostic model. Significant differences in overall survival rate, immune cell infiltration status, and somatic mutations existed between the high and low-risk scores in BLCA patients. Finally, drug sensitivity analysis showed that high-risk patients benefited more from immunotherapy and chemotherapy drugs.ConclusionThis study explores the importance of necroptosis in the prognosis of patients with BLCA, and the prognostic features associated with necroptosis that we identified can serve as new biomarkers to help develop more precise treatment strategies.https://www.frontiersin.org/articles/10.3389/fmolb.2024.1493411/fullBLCAnecroptosistumor microenvironment (TME)prognostic modeltreatment response
spellingShingle Dongnuan Yao
Dongnuan Yao
Dongnuan Yao
Weitao Yu
Weitao Yu
Weitao Yu
Xueming Ma
Xueming Ma
Xueming Ma
Junqiang Tian
Junqiang Tian
Junqiang Tian
A novel necroptosis-related genes signature to predict prognosis and treatment response in bladder cancer
Frontiers in Molecular Biosciences
BLCA
necroptosis
tumor microenvironment (TME)
prognostic model
treatment response
title A novel necroptosis-related genes signature to predict prognosis and treatment response in bladder cancer
title_full A novel necroptosis-related genes signature to predict prognosis and treatment response in bladder cancer
title_fullStr A novel necroptosis-related genes signature to predict prognosis and treatment response in bladder cancer
title_full_unstemmed A novel necroptosis-related genes signature to predict prognosis and treatment response in bladder cancer
title_short A novel necroptosis-related genes signature to predict prognosis and treatment response in bladder cancer
title_sort novel necroptosis related genes signature to predict prognosis and treatment response in bladder cancer
topic BLCA
necroptosis
tumor microenvironment (TME)
prognostic model
treatment response
url https://www.frontiersin.org/articles/10.3389/fmolb.2024.1493411/full
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