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Construction of a prognostic model based on eight ubiquitination-related genes via machine learning and potential therapeutics analysis for cervical cancer

Introduction: Ubiquitination is involved in many biological processes and its predictive value for prognosis in cervical cancer is still unclear. Methods: To further explore the predictive value of the ubiquitination-related genes we obtained URGs from the Ubiquitin and Ubiquitin-like Conjugation Da...

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Autores principales: Hao, Yiping, Guy, Mutangala Muloye, Liu, Qingqing, Li, Ruowen, Mao, Zhonghao, Jiang, Nan, Wang, Bingyu, Cui, Baoxia, Zhang, Wenjing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10043205/
https://www.ncbi.nlm.nih.gov/pubmed/36999051
http://dx.doi.org/10.3389/fgene.2023.1142938
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author Hao, Yiping
Guy, Mutangala Muloye
Liu, Qingqing
Li, Ruowen
Mao, Zhonghao
Jiang, Nan
Wang, Bingyu
Cui, Baoxia
Zhang, Wenjing
author_facet Hao, Yiping
Guy, Mutangala Muloye
Liu, Qingqing
Li, Ruowen
Mao, Zhonghao
Jiang, Nan
Wang, Bingyu
Cui, Baoxia
Zhang, Wenjing
author_sort Hao, Yiping
collection PubMed
description Introduction: Ubiquitination is involved in many biological processes and its predictive value for prognosis in cervical cancer is still unclear. Methods: To further explore the predictive value of the ubiquitination-related genes we obtained URGs from the Ubiquitin and Ubiquitin-like Conjugation Database, analyzed datasets from The Cancer Genome Atlas and Gene Expression Omnibus databases, and then selected differentially expressed ubiquitination-related genes between normal and cancer tissues. Then, DURGs significantly associated with overall survival were selected through univariate Cox regression. Machine learning was further used to select the DURGs. Then, we constructed and validated a reliable prognostic gene signature by multivariate analysis. In addition, we predicted the substrate proteins of the signature genes and did a functional analysis to further understand the molecular biology mechanisms. The study provided new guidelines for evaluating cervical cancer prognosis and also suggested new directions for drug development. Results: By analyzing 1,390 URGs in GEO and TCGA databases, we obtained 175 DURGs. Our results showed 19 DURGs were related to prognosis. Finally, eight DURGs were identified via machine learning to construct the first ubiquitination prognostic gene signature. Patients were stratified into high-risk and low-risk groups and the prognosis was worse in the high-risk group. In addition, these gene protein levels were mostly consistent with their transcript level. According to the functional analysis of substrate proteins, the signature genes may be involved in cancer development through the transcription factor activity and the classical P53 pathway ubiquitination-related signaling pathways. Additionally, 71 small molecular compounds were identified as potential drugs. Conclusion: We systematically studied the influence of ubiquitination-related genes on prognosis in cervical cancer, established a prognostic model through a machine learning algorithm, and verified it. Also, our study provides a new treatment strategy for cervical cancer.
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spelling pubmed-100432052023-03-29 Construction of a prognostic model based on eight ubiquitination-related genes via machine learning and potential therapeutics analysis for cervical cancer Hao, Yiping Guy, Mutangala Muloye Liu, Qingqing Li, Ruowen Mao, Zhonghao Jiang, Nan Wang, Bingyu Cui, Baoxia Zhang, Wenjing Front Genet Genetics Introduction: Ubiquitination is involved in many biological processes and its predictive value for prognosis in cervical cancer is still unclear. Methods: To further explore the predictive value of the ubiquitination-related genes we obtained URGs from the Ubiquitin and Ubiquitin-like Conjugation Database, analyzed datasets from The Cancer Genome Atlas and Gene Expression Omnibus databases, and then selected differentially expressed ubiquitination-related genes between normal and cancer tissues. Then, DURGs significantly associated with overall survival were selected through univariate Cox regression. Machine learning was further used to select the DURGs. Then, we constructed and validated a reliable prognostic gene signature by multivariate analysis. In addition, we predicted the substrate proteins of the signature genes and did a functional analysis to further understand the molecular biology mechanisms. The study provided new guidelines for evaluating cervical cancer prognosis and also suggested new directions for drug development. Results: By analyzing 1,390 URGs in GEO and TCGA databases, we obtained 175 DURGs. Our results showed 19 DURGs were related to prognosis. Finally, eight DURGs were identified via machine learning to construct the first ubiquitination prognostic gene signature. Patients were stratified into high-risk and low-risk groups and the prognosis was worse in the high-risk group. In addition, these gene protein levels were mostly consistent with their transcript level. According to the functional analysis of substrate proteins, the signature genes may be involved in cancer development through the transcription factor activity and the classical P53 pathway ubiquitination-related signaling pathways. Additionally, 71 small molecular compounds were identified as potential drugs. Conclusion: We systematically studied the influence of ubiquitination-related genes on prognosis in cervical cancer, established a prognostic model through a machine learning algorithm, and verified it. Also, our study provides a new treatment strategy for cervical cancer. Frontiers Media S.A. 2023-03-14 /pmc/articles/PMC10043205/ /pubmed/36999051 http://dx.doi.org/10.3389/fgene.2023.1142938 Text en Copyright © 2023 Hao, Guy, Liu, Li, Mao, Jiang, Wang, Cui and Zhang. 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
Hao, Yiping
Guy, Mutangala Muloye
Liu, Qingqing
Li, Ruowen
Mao, Zhonghao
Jiang, Nan
Wang, Bingyu
Cui, Baoxia
Zhang, Wenjing
Construction of a prognostic model based on eight ubiquitination-related genes via machine learning and potential therapeutics analysis for cervical cancer
title Construction of a prognostic model based on eight ubiquitination-related genes via machine learning and potential therapeutics analysis for cervical cancer
title_full Construction of a prognostic model based on eight ubiquitination-related genes via machine learning and potential therapeutics analysis for cervical cancer
title_fullStr Construction of a prognostic model based on eight ubiquitination-related genes via machine learning and potential therapeutics analysis for cervical cancer
title_full_unstemmed Construction of a prognostic model based on eight ubiquitination-related genes via machine learning and potential therapeutics analysis for cervical cancer
title_short Construction of a prognostic model based on eight ubiquitination-related genes via machine learning and potential therapeutics analysis for cervical cancer
title_sort construction of a prognostic model based on eight ubiquitination-related genes via machine learning and potential therapeutics analysis for cervical cancer
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10043205/
https://www.ncbi.nlm.nih.gov/pubmed/36999051
http://dx.doi.org/10.3389/fgene.2023.1142938
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