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Identification of senescence-related subtypes, establishment of a prognosis model, and characterization of a tumor microenvironment infiltration in breast cancer

Breast cancer is a malignancy with the highest incidence and mortality in women worldwide. Senescence is a model of arrest in the cell cycle, which plays an important role in tumor progression, while the prognostic value of cellular senescence-related genes (SRGs) in evaluating immune infiltration a...

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Autores principales: Zhou, Yanling, Xiao, Liang, Long, Guo, Cao, Jing, Liu, Shuang, Tao, Yongguang, Zhou, Ledu, Tang, Jianing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9441960/
https://www.ncbi.nlm.nih.gov/pubmed/36072578
http://dx.doi.org/10.3389/fimmu.2022.921182
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author Zhou, Yanling
Xiao, Liang
Long, Guo
Cao, Jing
Liu, Shuang
Tao, Yongguang
Zhou, Ledu
Tang, Jianing
author_facet Zhou, Yanling
Xiao, Liang
Long, Guo
Cao, Jing
Liu, Shuang
Tao, Yongguang
Zhou, Ledu
Tang, Jianing
author_sort Zhou, Yanling
collection PubMed
description Breast cancer is a malignancy with the highest incidence and mortality in women worldwide. Senescence is a model of arrest in the cell cycle, which plays an important role in tumor progression, while the prognostic value of cellular senescence-related genes (SRGs) in evaluating immune infiltration and clinical outcomes of breast cancer needs further investigation. In the present study, we identified two distinct molecular subtypes according to the expression profiles of 278 SRGs. We further explored the dysregulated pathways between the two subtypes and constructed a microenvironmental landscape of breast cancer. Subsequently, we established a senescence-related scoring signature based on the expression of four SRGs in the training set (GSE21653) and validated its accuracy in two validation sets (GSE20685 and GSE25055). In the training set, patients in the high-risk group had a worse prognosis than patients in the low-risk group. Multivariate Cox regression analysis showed that risk score was an independent prognostic indicator. Receiver operating characteristic curve (ROC) analysis proved the predictive accuracy of the signature. The prognostic value of this signature was further confirmed in the validation sets. We also observed that a lower risk score was associated with a higher pathological response rate in patients with neoadjuvant chemotherapy. We next performed functional experiments to validate the results above. Our study demonstrated that these cellular senescence patterns effectively grouped patients at low or high risk of disease recurrence and revealed their potential roles in the tumor–immune–stromal microenvironment. These findings enhanced our understanding of the tumor immune microenvironment and provided new insights for improving the prognosis of breast cancer patients.
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spelling pubmed-94419602022-09-06 Identification of senescence-related subtypes, establishment of a prognosis model, and characterization of a tumor microenvironment infiltration in breast cancer Zhou, Yanling Xiao, Liang Long, Guo Cao, Jing Liu, Shuang Tao, Yongguang Zhou, Ledu Tang, Jianing Front Immunol Immunology Breast cancer is a malignancy with the highest incidence and mortality in women worldwide. Senescence is a model of arrest in the cell cycle, which plays an important role in tumor progression, while the prognostic value of cellular senescence-related genes (SRGs) in evaluating immune infiltration and clinical outcomes of breast cancer needs further investigation. In the present study, we identified two distinct molecular subtypes according to the expression profiles of 278 SRGs. We further explored the dysregulated pathways between the two subtypes and constructed a microenvironmental landscape of breast cancer. Subsequently, we established a senescence-related scoring signature based on the expression of four SRGs in the training set (GSE21653) and validated its accuracy in two validation sets (GSE20685 and GSE25055). In the training set, patients in the high-risk group had a worse prognosis than patients in the low-risk group. Multivariate Cox regression analysis showed that risk score was an independent prognostic indicator. Receiver operating characteristic curve (ROC) analysis proved the predictive accuracy of the signature. The prognostic value of this signature was further confirmed in the validation sets. We also observed that a lower risk score was associated with a higher pathological response rate in patients with neoadjuvant chemotherapy. We next performed functional experiments to validate the results above. Our study demonstrated that these cellular senescence patterns effectively grouped patients at low or high risk of disease recurrence and revealed their potential roles in the tumor–immune–stromal microenvironment. These findings enhanced our understanding of the tumor immune microenvironment and provided new insights for improving the prognosis of breast cancer patients. Frontiers Media S.A. 2022-08-22 /pmc/articles/PMC9441960/ /pubmed/36072578 http://dx.doi.org/10.3389/fimmu.2022.921182 Text en Copyright © 2022 Zhou, Xiao, Long, Cao, Liu, Tao, Zhou and Tang 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
Zhou, Yanling
Xiao, Liang
Long, Guo
Cao, Jing
Liu, Shuang
Tao, Yongguang
Zhou, Ledu
Tang, Jianing
Identification of senescence-related subtypes, establishment of a prognosis model, and characterization of a tumor microenvironment infiltration in breast cancer
title Identification of senescence-related subtypes, establishment of a prognosis model, and characterization of a tumor microenvironment infiltration in breast cancer
title_full Identification of senescence-related subtypes, establishment of a prognosis model, and characterization of a tumor microenvironment infiltration in breast cancer
title_fullStr Identification of senescence-related subtypes, establishment of a prognosis model, and characterization of a tumor microenvironment infiltration in breast cancer
title_full_unstemmed Identification of senescence-related subtypes, establishment of a prognosis model, and characterization of a tumor microenvironment infiltration in breast cancer
title_short Identification of senescence-related subtypes, establishment of a prognosis model, and characterization of a tumor microenvironment infiltration in breast cancer
title_sort identification of senescence-related subtypes, establishment of a prognosis model, and characterization of a tumor microenvironment infiltration in breast cancer
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9441960/
https://www.ncbi.nlm.nih.gov/pubmed/36072578
http://dx.doi.org/10.3389/fimmu.2022.921182
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