Cargando…

Construction and Validation of a 15-Top-prognostic-gene-based Signature to Indicate the Dichotomized Clinical Outcome and Response to Targeted Therapy for Bladder Cancer Patients

The clinical outcome of heterogeneous bladder cancer (BCa) is impacted by varying molecular characteristics and clinical features, and new molecular classification is necessary to recognize patients with dichotomized prognosis. We enrolled a total of 568 BCa patients from the TCGA-BLCA and GSE13507...

Descripción completa

Detalles Bibliográficos
Autores principales: Gu, Hongbing, Liang, Chaozhao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009041/
https://www.ncbi.nlm.nih.gov/pubmed/35433683
http://dx.doi.org/10.3389/fcell.2022.725024
_version_ 1784687189903278080
author Gu, Hongbing
Liang, Chaozhao
author_facet Gu, Hongbing
Liang, Chaozhao
author_sort Gu, Hongbing
collection PubMed
description The clinical outcome of heterogeneous bladder cancer (BCa) is impacted by varying molecular characteristics and clinical features, and new molecular classification is necessary to recognize patients with dichotomized prognosis. We enrolled a total of 568 BCa patients from the TCGA-BLCA and GSE13507 cohorts. A total of 107 candidate genes, which were mostly involved in the extracellular matrix-associated pathway, were first selected through the consensus value of the area under the receiver operating characteristic curve (AUC). Furthermore, absolute shrinkage and selection operation regression analysis was implemented to reveal the 15 genes and establish the prognostic signature. The newly defined prognostic signature could precisely separate BCa patients into subgroups with favorable and poor prognosis in the training TCGA-BLCA cohort (p < 0.001, HR = 2.41, and 95% CI: 1.76–3.29), as well as the testing GSE13507 cohort (p < 0.001, HR = 7.32, and 95% CI: 1.76–3.29) and external validation E-MTAB-4321 cohort (p < 0.001, HR = 10.56, 95% CI: 3.208–34.731). Multivariate Cox analysis involving the signature and clinical features indicated that the signature is an independent factor for the prediction of BCa prognosis. We also explored potential targeted therapy for BCa patients with high- or low-risk scores and found that patients with high risk were more suitable for chemotherapy with gemcitabine, doxorubicin, cisplatin, paclitaxel, and vinblastine (all p < 0.05), but anti-PD-L1 therapy was useless. We knocked down HEYL with siRNAs in T24 and 5,637 cells, and observed the decreased protein level of HEYL, and inhibited cell viability and cell invasion. In summary, we proposed and validated a 15-top-prognostic gene-based signature to indicate the dichotomized prognosis and response to targeted therapy.
format Online
Article
Text
id pubmed-9009041
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-90090412022-04-15 Construction and Validation of a 15-Top-prognostic-gene-based Signature to Indicate the Dichotomized Clinical Outcome and Response to Targeted Therapy for Bladder Cancer Patients Gu, Hongbing Liang, Chaozhao Front Cell Dev Biol Cell and Developmental Biology The clinical outcome of heterogeneous bladder cancer (BCa) is impacted by varying molecular characteristics and clinical features, and new molecular classification is necessary to recognize patients with dichotomized prognosis. We enrolled a total of 568 BCa patients from the TCGA-BLCA and GSE13507 cohorts. A total of 107 candidate genes, which were mostly involved in the extracellular matrix-associated pathway, were first selected through the consensus value of the area under the receiver operating characteristic curve (AUC). Furthermore, absolute shrinkage and selection operation regression analysis was implemented to reveal the 15 genes and establish the prognostic signature. The newly defined prognostic signature could precisely separate BCa patients into subgroups with favorable and poor prognosis in the training TCGA-BLCA cohort (p < 0.001, HR = 2.41, and 95% CI: 1.76–3.29), as well as the testing GSE13507 cohort (p < 0.001, HR = 7.32, and 95% CI: 1.76–3.29) and external validation E-MTAB-4321 cohort (p < 0.001, HR = 10.56, 95% CI: 3.208–34.731). Multivariate Cox analysis involving the signature and clinical features indicated that the signature is an independent factor for the prediction of BCa prognosis. We also explored potential targeted therapy for BCa patients with high- or low-risk scores and found that patients with high risk were more suitable for chemotherapy with gemcitabine, doxorubicin, cisplatin, paclitaxel, and vinblastine (all p < 0.05), but anti-PD-L1 therapy was useless. We knocked down HEYL with siRNAs in T24 and 5,637 cells, and observed the decreased protein level of HEYL, and inhibited cell viability and cell invasion. In summary, we proposed and validated a 15-top-prognostic gene-based signature to indicate the dichotomized prognosis and response to targeted therapy. Frontiers Media S.A. 2022-03-31 /pmc/articles/PMC9009041/ /pubmed/35433683 http://dx.doi.org/10.3389/fcell.2022.725024 Text en Copyright © 2022 Gu and Liang. 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 Cell and Developmental Biology
Gu, Hongbing
Liang, Chaozhao
Construction and Validation of a 15-Top-prognostic-gene-based Signature to Indicate the Dichotomized Clinical Outcome and Response to Targeted Therapy for Bladder Cancer Patients
title Construction and Validation of a 15-Top-prognostic-gene-based Signature to Indicate the Dichotomized Clinical Outcome and Response to Targeted Therapy for Bladder Cancer Patients
title_full Construction and Validation of a 15-Top-prognostic-gene-based Signature to Indicate the Dichotomized Clinical Outcome and Response to Targeted Therapy for Bladder Cancer Patients
title_fullStr Construction and Validation of a 15-Top-prognostic-gene-based Signature to Indicate the Dichotomized Clinical Outcome and Response to Targeted Therapy for Bladder Cancer Patients
title_full_unstemmed Construction and Validation of a 15-Top-prognostic-gene-based Signature to Indicate the Dichotomized Clinical Outcome and Response to Targeted Therapy for Bladder Cancer Patients
title_short Construction and Validation of a 15-Top-prognostic-gene-based Signature to Indicate the Dichotomized Clinical Outcome and Response to Targeted Therapy for Bladder Cancer Patients
title_sort construction and validation of a 15-top-prognostic-gene-based signature to indicate the dichotomized clinical outcome and response to targeted therapy for bladder cancer patients
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009041/
https://www.ncbi.nlm.nih.gov/pubmed/35433683
http://dx.doi.org/10.3389/fcell.2022.725024
work_keys_str_mv AT guhongbing constructionandvalidationofa15topprognosticgenebasedsignaturetoindicatethedichotomizedclinicaloutcomeandresponsetotargetedtherapyforbladdercancerpatients
AT liangchaozhao constructionandvalidationofa15topprognosticgenebasedsignaturetoindicatethedichotomizedclinicaloutcomeandresponsetotargetedtherapyforbladdercancerpatients