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Integrated bioinformatic analysis identified a novel prognostic pan-programmed cell death signature for bladder cancer

Programmed cell death (PCD) refers to a molecularly regulated form of cell death that functions as an essential anticancer defense mechanism and serves as a target of anticancer therapies. Multiple types of PCD comprehensively regulate tumorigenesis and tumor progression and metastasis. However, a s...

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Autores principales: Zhang, Lusi, Peng, Mou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9728529/
https://www.ncbi.nlm.nih.gov/pubmed/36505448
http://dx.doi.org/10.3389/fimmu.2022.1030097
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author Zhang, Lusi
Peng, Mou
author_facet Zhang, Lusi
Peng, Mou
author_sort Zhang, Lusi
collection PubMed
description Programmed cell death (PCD) refers to a molecularly regulated form of cell death that functions as an essential anticancer defense mechanism and serves as a target of anticancer therapies. Multiple types of PCD comprehensively regulate tumorigenesis and tumor progression and metastasis. However, a systemic exploration of the multiple types of PCD in cancers, especially bladder cancer, is lacking. In this study, we evaluated the expression pattern of genes associated with multiple types of PCD in bladder cancer using the “ssGSEA” method and conceptualized the multiple types of PCD as being collectively involved in “Pan-PCD”. Based on the differentially expressed genes related to Pan-PCD, we developed a Pan-PCD-related prognostic signature (PPRPS) to predict patient prognosis via univariate and multivariate Cox regression analysis. The PPRPS is an independent prognostic factor, and the AUC (Area Under Curve) for 3-year overall survival was 0.748. Combined with age and stage, PPRPS displayed excellent predictive ability. Based on the PPRPS, higher levels of immune cell infiltration, tumor microenvironment, and immune checkpoint molecules were observed in the high-PPRPS group. Furthermore, PPRPS enabled accurate risk prediction for metastatic urothelial carcinoma after anti-PD-L1 monoclonal antibody treatment. Patients in the high-PPRPS group had poor prognoses. Docetaxel, staurosporine, and luminespib were identified as potentially effective drugs for high-PPRPS bladder cancer patients. In summary, we developed the Pan-PCD signature to improve the accuracy of bladder cancer prognostic predictions and to provide a novel classification method to guide treatment selection.
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spelling pubmed-97285292022-12-08 Integrated bioinformatic analysis identified a novel prognostic pan-programmed cell death signature for bladder cancer Zhang, Lusi Peng, Mou Front Immunol Immunology Programmed cell death (PCD) refers to a molecularly regulated form of cell death that functions as an essential anticancer defense mechanism and serves as a target of anticancer therapies. Multiple types of PCD comprehensively regulate tumorigenesis and tumor progression and metastasis. However, a systemic exploration of the multiple types of PCD in cancers, especially bladder cancer, is lacking. In this study, we evaluated the expression pattern of genes associated with multiple types of PCD in bladder cancer using the “ssGSEA” method and conceptualized the multiple types of PCD as being collectively involved in “Pan-PCD”. Based on the differentially expressed genes related to Pan-PCD, we developed a Pan-PCD-related prognostic signature (PPRPS) to predict patient prognosis via univariate and multivariate Cox regression analysis. The PPRPS is an independent prognostic factor, and the AUC (Area Under Curve) for 3-year overall survival was 0.748. Combined with age and stage, PPRPS displayed excellent predictive ability. Based on the PPRPS, higher levels of immune cell infiltration, tumor microenvironment, and immune checkpoint molecules were observed in the high-PPRPS group. Furthermore, PPRPS enabled accurate risk prediction for metastatic urothelial carcinoma after anti-PD-L1 monoclonal antibody treatment. Patients in the high-PPRPS group had poor prognoses. Docetaxel, staurosporine, and luminespib were identified as potentially effective drugs for high-PPRPS bladder cancer patients. In summary, we developed the Pan-PCD signature to improve the accuracy of bladder cancer prognostic predictions and to provide a novel classification method to guide treatment selection. Frontiers Media S.A. 2022-11-23 /pmc/articles/PMC9728529/ /pubmed/36505448 http://dx.doi.org/10.3389/fimmu.2022.1030097 Text en Copyright © 2022 Zhang and Peng https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zhang, Lusi
Peng, Mou
Integrated bioinformatic analysis identified a novel prognostic pan-programmed cell death signature for bladder cancer
title Integrated bioinformatic analysis identified a novel prognostic pan-programmed cell death signature for bladder cancer
title_full Integrated bioinformatic analysis identified a novel prognostic pan-programmed cell death signature for bladder cancer
title_fullStr Integrated bioinformatic analysis identified a novel prognostic pan-programmed cell death signature for bladder cancer
title_full_unstemmed Integrated bioinformatic analysis identified a novel prognostic pan-programmed cell death signature for bladder cancer
title_short Integrated bioinformatic analysis identified a novel prognostic pan-programmed cell death signature for bladder cancer
title_sort integrated bioinformatic analysis identified a novel prognostic pan-programmed cell death signature for bladder cancer
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9728529/
https://www.ncbi.nlm.nih.gov/pubmed/36505448
http://dx.doi.org/10.3389/fimmu.2022.1030097
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