Cargando…

A senescence-associated signature refines the classification of different modification patterns and characterization of tumor immune microenvironment infiltration in triple-negative breast cancer

Background: Recent studies have found that senescence-associated genes play a significant role in cancer biological processes. We aimed to analyze the characteristics and role of senescence-associated genes in triple-negative breast cancer (TNBC). Methods: We systematically screened senescence-assoc...

Descripción completa

Detalles Bibliográficos
Autores principales: Huang, Renhong, Wang, Han, Hong, Jin, Wang, Zheng, Wu, Jiayi, Huang, Ou, He, Jianrong, Chen, Weiguo, Li, Yafen, Chen, Xiaosong, Shen, Kunwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10213971/
https://www.ncbi.nlm.nih.gov/pubmed/37251343
http://dx.doi.org/10.3389/fphar.2023.1191910
_version_ 1785047741687136256
author Huang, Renhong
Wang, Han
Hong, Jin
Wang, Zheng
Wu, Jiayi
Huang, Ou
He, Jianrong
Chen, Weiguo
Li, Yafen
Chen, Xiaosong
Shen, Kunwei
author_facet Huang, Renhong
Wang, Han
Hong, Jin
Wang, Zheng
Wu, Jiayi
Huang, Ou
He, Jianrong
Chen, Weiguo
Li, Yafen
Chen, Xiaosong
Shen, Kunwei
author_sort Huang, Renhong
collection PubMed
description Background: Recent studies have found that senescence-associated genes play a significant role in cancer biological processes. We aimed to analyze the characteristics and role of senescence-associated genes in triple-negative breast cancer (TNBC). Methods: We systematically screened senescence-associated secretory phenotype (SASP) genes based on the gene expression information in the TCGA database. According to the expression levels of senescence-associated genes, TNBC was classified into two subtypes, namely, TNBCSASP1 and TNBCSASP2, using an unsupervised cluster algorithm. We then performed gene expression, enrichment pathway, immune infiltration, mutational profile characterization, drug sensitivity and prognostic value analyses for the two subtypes. The reliability and prognostic predictive utility of this classification model were validated. The most prognostically relevant gene, FAM3B, was comprehensively identified and validated by tissue microarray in TNBC. Results: TNBC was classified into two senescence-associated subtypes, TNBCSASP1 and TNBCSASP2, based on the set of senescence-associated secretory phenotype genes, among which the TNBCSASP1 subtype had a poor prognosis. The TNBCSASP1 subtype was immunosuppressed, with suppressed immune-related signaling pathways and low immune cell infiltration. The effect of the mutation on the TP53 and TGF-β pathways could be related to the poor prognosis of the TNBCSASP1 subtype. Drug sensitivity analysis showed that AMG.706, CCT007093, and CHIR.99021 were potential targeted drugs for the TNBCSASP1 subtype. Finally, FAM3B was a key biomarker affecting the prognosis of patients with triple-negative breast cancer. Compared to normal breast tissue, the expression of FAM3B was reduced in triple-negative breast cancer. Survival analysis showed that overall survival was significantly shorter in triple-negative breast cancer patients with high FAM3B expression. Conclusion: A senescence-associated signature with different modification patterns has critical potential for providing a better understanding of TNBC biological processes, and FAM3B might serve as an applicable target for TNBC therapy.
format Online
Article
Text
id pubmed-10213971
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-102139712023-05-27 A senescence-associated signature refines the classification of different modification patterns and characterization of tumor immune microenvironment infiltration in triple-negative breast cancer Huang, Renhong Wang, Han Hong, Jin Wang, Zheng Wu, Jiayi Huang, Ou He, Jianrong Chen, Weiguo Li, Yafen Chen, Xiaosong Shen, Kunwei Front Pharmacol Pharmacology Background: Recent studies have found that senescence-associated genes play a significant role in cancer biological processes. We aimed to analyze the characteristics and role of senescence-associated genes in triple-negative breast cancer (TNBC). Methods: We systematically screened senescence-associated secretory phenotype (SASP) genes based on the gene expression information in the TCGA database. According to the expression levels of senescence-associated genes, TNBC was classified into two subtypes, namely, TNBCSASP1 and TNBCSASP2, using an unsupervised cluster algorithm. We then performed gene expression, enrichment pathway, immune infiltration, mutational profile characterization, drug sensitivity and prognostic value analyses for the two subtypes. The reliability and prognostic predictive utility of this classification model were validated. The most prognostically relevant gene, FAM3B, was comprehensively identified and validated by tissue microarray in TNBC. Results: TNBC was classified into two senescence-associated subtypes, TNBCSASP1 and TNBCSASP2, based on the set of senescence-associated secretory phenotype genes, among which the TNBCSASP1 subtype had a poor prognosis. The TNBCSASP1 subtype was immunosuppressed, with suppressed immune-related signaling pathways and low immune cell infiltration. The effect of the mutation on the TP53 and TGF-β pathways could be related to the poor prognosis of the TNBCSASP1 subtype. Drug sensitivity analysis showed that AMG.706, CCT007093, and CHIR.99021 were potential targeted drugs for the TNBCSASP1 subtype. Finally, FAM3B was a key biomarker affecting the prognosis of patients with triple-negative breast cancer. Compared to normal breast tissue, the expression of FAM3B was reduced in triple-negative breast cancer. Survival analysis showed that overall survival was significantly shorter in triple-negative breast cancer patients with high FAM3B expression. Conclusion: A senescence-associated signature with different modification patterns has critical potential for providing a better understanding of TNBC biological processes, and FAM3B might serve as an applicable target for TNBC therapy. Frontiers Media S.A. 2023-05-11 /pmc/articles/PMC10213971/ /pubmed/37251343 http://dx.doi.org/10.3389/fphar.2023.1191910 Text en Copyright © 2023 Huang, Wang, Hong, Wang, Wu, Huang, He, Chen, Li, Chen and Shen. 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 Pharmacology
Huang, Renhong
Wang, Han
Hong, Jin
Wang, Zheng
Wu, Jiayi
Huang, Ou
He, Jianrong
Chen, Weiguo
Li, Yafen
Chen, Xiaosong
Shen, Kunwei
A senescence-associated signature refines the classification of different modification patterns and characterization of tumor immune microenvironment infiltration in triple-negative breast cancer
title A senescence-associated signature refines the classification of different modification patterns and characterization of tumor immune microenvironment infiltration in triple-negative breast cancer
title_full A senescence-associated signature refines the classification of different modification patterns and characterization of tumor immune microenvironment infiltration in triple-negative breast cancer
title_fullStr A senescence-associated signature refines the classification of different modification patterns and characterization of tumor immune microenvironment infiltration in triple-negative breast cancer
title_full_unstemmed A senescence-associated signature refines the classification of different modification patterns and characterization of tumor immune microenvironment infiltration in triple-negative breast cancer
title_short A senescence-associated signature refines the classification of different modification patterns and characterization of tumor immune microenvironment infiltration in triple-negative breast cancer
title_sort senescence-associated signature refines the classification of different modification patterns and characterization of tumor immune microenvironment infiltration in triple-negative breast cancer
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10213971/
https://www.ncbi.nlm.nih.gov/pubmed/37251343
http://dx.doi.org/10.3389/fphar.2023.1191910
work_keys_str_mv AT huangrenhong asenescenceassociatedsignaturerefinestheclassificationofdifferentmodificationpatternsandcharacterizationoftumorimmunemicroenvironmentinfiltrationintriplenegativebreastcancer
AT wanghan asenescenceassociatedsignaturerefinestheclassificationofdifferentmodificationpatternsandcharacterizationoftumorimmunemicroenvironmentinfiltrationintriplenegativebreastcancer
AT hongjin asenescenceassociatedsignaturerefinestheclassificationofdifferentmodificationpatternsandcharacterizationoftumorimmunemicroenvironmentinfiltrationintriplenegativebreastcancer
AT wangzheng asenescenceassociatedsignaturerefinestheclassificationofdifferentmodificationpatternsandcharacterizationoftumorimmunemicroenvironmentinfiltrationintriplenegativebreastcancer
AT wujiayi asenescenceassociatedsignaturerefinestheclassificationofdifferentmodificationpatternsandcharacterizationoftumorimmunemicroenvironmentinfiltrationintriplenegativebreastcancer
AT huangou asenescenceassociatedsignaturerefinestheclassificationofdifferentmodificationpatternsandcharacterizationoftumorimmunemicroenvironmentinfiltrationintriplenegativebreastcancer
AT hejianrong asenescenceassociatedsignaturerefinestheclassificationofdifferentmodificationpatternsandcharacterizationoftumorimmunemicroenvironmentinfiltrationintriplenegativebreastcancer
AT chenweiguo asenescenceassociatedsignaturerefinestheclassificationofdifferentmodificationpatternsandcharacterizationoftumorimmunemicroenvironmentinfiltrationintriplenegativebreastcancer
AT liyafen asenescenceassociatedsignaturerefinestheclassificationofdifferentmodificationpatternsandcharacterizationoftumorimmunemicroenvironmentinfiltrationintriplenegativebreastcancer
AT chenxiaosong asenescenceassociatedsignaturerefinestheclassificationofdifferentmodificationpatternsandcharacterizationoftumorimmunemicroenvironmentinfiltrationintriplenegativebreastcancer
AT shenkunwei asenescenceassociatedsignaturerefinestheclassificationofdifferentmodificationpatternsandcharacterizationoftumorimmunemicroenvironmentinfiltrationintriplenegativebreastcancer
AT huangrenhong senescenceassociatedsignaturerefinestheclassificationofdifferentmodificationpatternsandcharacterizationoftumorimmunemicroenvironmentinfiltrationintriplenegativebreastcancer
AT wanghan senescenceassociatedsignaturerefinestheclassificationofdifferentmodificationpatternsandcharacterizationoftumorimmunemicroenvironmentinfiltrationintriplenegativebreastcancer
AT hongjin senescenceassociatedsignaturerefinestheclassificationofdifferentmodificationpatternsandcharacterizationoftumorimmunemicroenvironmentinfiltrationintriplenegativebreastcancer
AT wangzheng senescenceassociatedsignaturerefinestheclassificationofdifferentmodificationpatternsandcharacterizationoftumorimmunemicroenvironmentinfiltrationintriplenegativebreastcancer
AT wujiayi senescenceassociatedsignaturerefinestheclassificationofdifferentmodificationpatternsandcharacterizationoftumorimmunemicroenvironmentinfiltrationintriplenegativebreastcancer
AT huangou senescenceassociatedsignaturerefinestheclassificationofdifferentmodificationpatternsandcharacterizationoftumorimmunemicroenvironmentinfiltrationintriplenegativebreastcancer
AT hejianrong senescenceassociatedsignaturerefinestheclassificationofdifferentmodificationpatternsandcharacterizationoftumorimmunemicroenvironmentinfiltrationintriplenegativebreastcancer
AT chenweiguo senescenceassociatedsignaturerefinestheclassificationofdifferentmodificationpatternsandcharacterizationoftumorimmunemicroenvironmentinfiltrationintriplenegativebreastcancer
AT liyafen senescenceassociatedsignaturerefinestheclassificationofdifferentmodificationpatternsandcharacterizationoftumorimmunemicroenvironmentinfiltrationintriplenegativebreastcancer
AT chenxiaosong senescenceassociatedsignaturerefinestheclassificationofdifferentmodificationpatternsandcharacterizationoftumorimmunemicroenvironmentinfiltrationintriplenegativebreastcancer
AT shenkunwei senescenceassociatedsignaturerefinestheclassificationofdifferentmodificationpatternsandcharacterizationoftumorimmunemicroenvironmentinfiltrationintriplenegativebreastcancer