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Development and Validation of a Six-Gene Prognostic Signature for Bladder Cancer

Human bladder cancer (BCa) is the most common urogenital system malignancy. Patients with BCa have limited treatment efficacy in clinical practice. Novel biomarkers could provide more crucial information conferring to cancer diagnosis, treatment, and prognosis. Here, we aimed to explore and identify...

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Autores principales: Xu, Fei, Tang, Qianqian, Wang, Yejinpeng, Wang, Gang, Qian, Kaiyu, Ju, Lingao, Xiao, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8685517/
https://www.ncbi.nlm.nih.gov/pubmed/34938313
http://dx.doi.org/10.3389/fgene.2021.758612
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author Xu, Fei
Tang, Qianqian
Wang, Yejinpeng
Wang, Gang
Qian, Kaiyu
Ju, Lingao
Xiao, Yu
author_facet Xu, Fei
Tang, Qianqian
Wang, Yejinpeng
Wang, Gang
Qian, Kaiyu
Ju, Lingao
Xiao, Yu
author_sort Xu, Fei
collection PubMed
description Human bladder cancer (BCa) is the most common urogenital system malignancy. Patients with BCa have limited treatment efficacy in clinical practice. Novel biomarkers could provide more crucial information conferring to cancer diagnosis, treatment, and prognosis. Here, we aimed to explore and identify novel biomarkers associated with cancer-specific survival of patients with BCa to build a prognostic signature. Based on univariate Cox regression, Lasso regression, and multivariate Cox regression analysis, we conducted an integrated analysis in the training set (GSE32894) and established a six-gene signature to predict the cancer-specific survival for human BCa. The six genes were Cyclin Dependent Kinase 4 (CDK4), E2F Transcription Factor 7 (E2F7), Collagen Type XI Alpha 1 Chain (COL11A1), Bradykinin Receptor B2 (BDKRB2), Yip1 Interacting Factor Homolog B (YIF1B), and Zinc Finger Protein 415 (ZNF415). Then, we validated the prognostic value of the model by using two other datasets (GSE13507 and TCGA). Also, we conducted univariate and multivariate Cox regression analyses, and results indicated that the six-gene signature was an independent prognostic factor of cancer-specific survival of patients with BCa. Functional analysis was performed based on the differentially expressed genes of low- and high-risk patients, and we found that they were enriched in lipid metabolic and cell division-related biological processes. Meanwhile, the gene set enrichment analysis (GSEA) revealed that high-risk samples were enriched in cell cycle and cancer-related pathways [G2/M checkpoint, E2F targets, mitotic spindle, mTOR signaling, spermatogenesis, epithelial–mesenchymal transition (EMT), DNA repair, PI3K/AKT/mTOR signaling, unfolded protein response (UPR), and MYC targets V2]. Lastly, we detected the relative expression of each signature in BCa cell lines by quantitative real-time PCR (qRT-PCR). As far as we know, currently, the present study is the first research that developed and validated a cancer-specific survival prognostic index based on three independent cohorts. The results revealed that this six-gene signature has a predictive ability for cancer-specific prognosis. Moreover, we also verified the relative expression of these six signatures between the bladder cell line and four BCa cell lines by qRT-PCR. Nevertheless, experiments to further explore the function of six genes are lacking.
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spelling pubmed-86855172021-12-21 Development and Validation of a Six-Gene Prognostic Signature for Bladder Cancer Xu, Fei Tang, Qianqian Wang, Yejinpeng Wang, Gang Qian, Kaiyu Ju, Lingao Xiao, Yu Front Genet Genetics Human bladder cancer (BCa) is the most common urogenital system malignancy. Patients with BCa have limited treatment efficacy in clinical practice. Novel biomarkers could provide more crucial information conferring to cancer diagnosis, treatment, and prognosis. Here, we aimed to explore and identify novel biomarkers associated with cancer-specific survival of patients with BCa to build a prognostic signature. Based on univariate Cox regression, Lasso regression, and multivariate Cox regression analysis, we conducted an integrated analysis in the training set (GSE32894) and established a six-gene signature to predict the cancer-specific survival for human BCa. The six genes were Cyclin Dependent Kinase 4 (CDK4), E2F Transcription Factor 7 (E2F7), Collagen Type XI Alpha 1 Chain (COL11A1), Bradykinin Receptor B2 (BDKRB2), Yip1 Interacting Factor Homolog B (YIF1B), and Zinc Finger Protein 415 (ZNF415). Then, we validated the prognostic value of the model by using two other datasets (GSE13507 and TCGA). Also, we conducted univariate and multivariate Cox regression analyses, and results indicated that the six-gene signature was an independent prognostic factor of cancer-specific survival of patients with BCa. Functional analysis was performed based on the differentially expressed genes of low- and high-risk patients, and we found that they were enriched in lipid metabolic and cell division-related biological processes. Meanwhile, the gene set enrichment analysis (GSEA) revealed that high-risk samples were enriched in cell cycle and cancer-related pathways [G2/M checkpoint, E2F targets, mitotic spindle, mTOR signaling, spermatogenesis, epithelial–mesenchymal transition (EMT), DNA repair, PI3K/AKT/mTOR signaling, unfolded protein response (UPR), and MYC targets V2]. Lastly, we detected the relative expression of each signature in BCa cell lines by quantitative real-time PCR (qRT-PCR). As far as we know, currently, the present study is the first research that developed and validated a cancer-specific survival prognostic index based on three independent cohorts. The results revealed that this six-gene signature has a predictive ability for cancer-specific prognosis. Moreover, we also verified the relative expression of these six signatures between the bladder cell line and four BCa cell lines by qRT-PCR. Nevertheless, experiments to further explore the function of six genes are lacking. Frontiers Media S.A. 2021-12-06 /pmc/articles/PMC8685517/ /pubmed/34938313 http://dx.doi.org/10.3389/fgene.2021.758612 Text en Copyright © 2021 Xu, Tang, Wang, Wang, Qian, Ju and Xiao. 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 Genetics
Xu, Fei
Tang, Qianqian
Wang, Yejinpeng
Wang, Gang
Qian, Kaiyu
Ju, Lingao
Xiao, Yu
Development and Validation of a Six-Gene Prognostic Signature for Bladder Cancer
title Development and Validation of a Six-Gene Prognostic Signature for Bladder Cancer
title_full Development and Validation of a Six-Gene Prognostic Signature for Bladder Cancer
title_fullStr Development and Validation of a Six-Gene Prognostic Signature for Bladder Cancer
title_full_unstemmed Development and Validation of a Six-Gene Prognostic Signature for Bladder Cancer
title_short Development and Validation of a Six-Gene Prognostic Signature for Bladder Cancer
title_sort development and validation of a six-gene prognostic signature for bladder cancer
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8685517/
https://www.ncbi.nlm.nih.gov/pubmed/34938313
http://dx.doi.org/10.3389/fgene.2021.758612
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