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Development and Validation of a Tumor Mutation Burden-Related Immune Prognostic Signature for Ovarian Cancers

Ovarian cancer (OC), one of the most common malignancies of the female reproductive system, is characterized by high incidence and poor prognosis. Tumor mutation burden (TMB), as an important biomarker that can represent the degree of tumor mutation, is emerging as a key indicator for predicting the...

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Autores principales: Cui, Mengjing, Xia, Qianqian, Zhang, Xing, Yan, Wenjing, Meng, Dan, Xie, Shuqian, Shen, Siyuan, Jin, Hua, Wang, Shizhi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8787320/
https://www.ncbi.nlm.nih.gov/pubmed/35087563
http://dx.doi.org/10.3389/fgene.2021.688207
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author Cui, Mengjing
Xia, Qianqian
Zhang, Xing
Yan, Wenjing
Meng, Dan
Xie, Shuqian
Shen, Siyuan
Jin, Hua
Wang, Shizhi
author_facet Cui, Mengjing
Xia, Qianqian
Zhang, Xing
Yan, Wenjing
Meng, Dan
Xie, Shuqian
Shen, Siyuan
Jin, Hua
Wang, Shizhi
author_sort Cui, Mengjing
collection PubMed
description Ovarian cancer (OC), one of the most common malignancies of the female reproductive system, is characterized by high incidence and poor prognosis. Tumor mutation burden (TMB), as an important biomarker that can represent the degree of tumor mutation, is emerging as a key indicator for predicting the efficacy of tumor immunotherapy. In our study, the gene expression profiles of OC were downloaded from TCGA and GEO databases. Subsequently, we analyzed the prognostic value of TMB in OC and found that a higher TMB score was significantly associated with a better prognosis (p = 0.004). According to the median score of TMB, 9 key TMB related immune prognostic genes were selected by LASSO regression for constructing a TMB associated immune risk score (TMB-IRS) signature, which can effectively predict the prognosis of OC patients (HR = 2.32, 95% CI = 1.68–3.32; AUC = 0.754). Interestingly, TMB-IRS is also closely related to the level of immune cell infiltration and immune checkpoint molecules (PD1, PD-L1, CTLA4, PD-L2) in OC. Furthermore, the nomogram combined with TMB-IRS and a variety of clinicopathological features can more comprehensively evaluate the prognosis of patients. In conclusion, we explored the relationship between TMB and prognosis and validated the TMB-IRS signature based on TMB score in an independent database (HR = 1.60, 95% CI = 1.13–2.27; AUC = 0.639), which may serve as a novel biomarker for predicting OC prognosis as well as possible therapeutic targets.
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spelling pubmed-87873202022-01-26 Development and Validation of a Tumor Mutation Burden-Related Immune Prognostic Signature for Ovarian Cancers Cui, Mengjing Xia, Qianqian Zhang, Xing Yan, Wenjing Meng, Dan Xie, Shuqian Shen, Siyuan Jin, Hua Wang, Shizhi Front Genet Genetics Ovarian cancer (OC), one of the most common malignancies of the female reproductive system, is characterized by high incidence and poor prognosis. Tumor mutation burden (TMB), as an important biomarker that can represent the degree of tumor mutation, is emerging as a key indicator for predicting the efficacy of tumor immunotherapy. In our study, the gene expression profiles of OC were downloaded from TCGA and GEO databases. Subsequently, we analyzed the prognostic value of TMB in OC and found that a higher TMB score was significantly associated with a better prognosis (p = 0.004). According to the median score of TMB, 9 key TMB related immune prognostic genes were selected by LASSO regression for constructing a TMB associated immune risk score (TMB-IRS) signature, which can effectively predict the prognosis of OC patients (HR = 2.32, 95% CI = 1.68–3.32; AUC = 0.754). Interestingly, TMB-IRS is also closely related to the level of immune cell infiltration and immune checkpoint molecules (PD1, PD-L1, CTLA4, PD-L2) in OC. Furthermore, the nomogram combined with TMB-IRS and a variety of clinicopathological features can more comprehensively evaluate the prognosis of patients. In conclusion, we explored the relationship between TMB and prognosis and validated the TMB-IRS signature based on TMB score in an independent database (HR = 1.60, 95% CI = 1.13–2.27; AUC = 0.639), which may serve as a novel biomarker for predicting OC prognosis as well as possible therapeutic targets. Frontiers Media S.A. 2022-01-11 /pmc/articles/PMC8787320/ /pubmed/35087563 http://dx.doi.org/10.3389/fgene.2021.688207 Text en Copyright © 2022 Cui, Xia, Zhang, Yan, Meng, Xie, Shen, Jin and Wang. 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
Cui, Mengjing
Xia, Qianqian
Zhang, Xing
Yan, Wenjing
Meng, Dan
Xie, Shuqian
Shen, Siyuan
Jin, Hua
Wang, Shizhi
Development and Validation of a Tumor Mutation Burden-Related Immune Prognostic Signature for Ovarian Cancers
title Development and Validation of a Tumor Mutation Burden-Related Immune Prognostic Signature for Ovarian Cancers
title_full Development and Validation of a Tumor Mutation Burden-Related Immune Prognostic Signature for Ovarian Cancers
title_fullStr Development and Validation of a Tumor Mutation Burden-Related Immune Prognostic Signature for Ovarian Cancers
title_full_unstemmed Development and Validation of a Tumor Mutation Burden-Related Immune Prognostic Signature for Ovarian Cancers
title_short Development and Validation of a Tumor Mutation Burden-Related Immune Prognostic Signature for Ovarian Cancers
title_sort development and validation of a tumor mutation burden-related immune prognostic signature for ovarian cancers
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8787320/
https://www.ncbi.nlm.nih.gov/pubmed/35087563
http://dx.doi.org/10.3389/fgene.2021.688207
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