TP53 Mutation Infers a Poor Prognosis and Is Correlated to Immunocytes Infiltration in Breast Cancer

Background: This study aimed to investigate the TP53 mutation, its potential immune features, its prognostic value, and its impact on immune infiltration in patients with breast cancer (BC).Methods: We downloaded the somatic mutation data and clinicopathologic features of BC patients from the TCGA G...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ziwen Zhang, Ran Hao, Qiusheng Guo, Sheyu Zhang, Xiaojia Wang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	TP53 mutation breast cancer immunocytes infiltration prognosis Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a5c845d4d34046febd184ba468ac3854
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a5c845d4d34046febd184ba468ac3854
record_format	dspace
spelling	oai:doaj.org-article:a5c845d4d34046febd184ba468ac38542021-12-01T18:47:08ZTP53 Mutation Infers a Poor Prognosis and Is Correlated to Immunocytes Infiltration in Breast Cancer2296-634X10.3389/fcell.2021.759154https://doaj.org/article/a5c845d4d34046febd184ba468ac38542021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.759154/fullhttps://doaj.org/toc/2296-634XBackground: This study aimed to investigate the TP53 mutation, its potential immune features, its prognostic value, and its impact on immune infiltration in patients with breast cancer (BC).Methods: We downloaded the somatic mutation data and clinicopathologic features of BC patients from the TCGA GDC database, UCSC Xena platform, and International Cancer Genome Consortium (ICGC) database. The association between the TP53 mutation, clinicopathology features, and overall survival (OS) in BC patients was analyzed. We evaluated the potential role of the TP53 mutation in the immune therapy response, including the tumor mutation burden (TMB), microsatellite instability (MSI), and tumor immune dysfunction and exclusion (TIDE). Moreover, ESTIMATE was employed to assess the ImmuneScore and StromalScore in BC patients. We also explored immunocyte infiltration related to the TP53 mutation and its potential mechanism. Immunohistochemistry (IHC) was performed to validate the association between the expression of CXCL1, CXCL10, and CCL20 and TP53 status.Results: We found that the TP53 mutation was significantly associated with the shorter OS (p = 0.038) and was also an independent predictive factor of OS for BC patients (p < 0.001). Compared to that in the wild type group, the TP53-mutant group showed a higher TMB value (P< 0.001), MSI value (p = 0.077), and TIDE value (p < 0.001) with respect to BC patient immunotherapy. In addition, the ImmuneScore and StromalScore were both significantly increased in the TP53-mutant group (ImmuneScore: p < 0.001; StromalScore: p = 0.003). The results of CIBERSORT suggested that the TP53 mutation significantly promoted the infiltration of Tregs, T helper cells, and M0-type macrophages. KEGG and GSEA enrichment results suggested that the IL-17 signaling pathway and antigen processing and presentation pathways were significantly enriched in the TP53-mutant group. Importantly, based on IHC results of immune-related hub-genes, the chemokines CXCL1, CXCL10, and CCL20 were significantly upregulated in the TP53-mutant group in BC patients.Conclusion: These results indicate that a TP53 mutation might serve as a biomarker for BC prognosis and is related to immunocyte infiltration in the tumor microenvironment.Ziwen ZhangZiwen ZhangRan HaoQiusheng GuoQiusheng GuoSheyu ZhangXiaojia WangXiaojia WangFrontiers Media S.A.articleTP53mutationbreast cancerimmunocytes infiltrationprognosisBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	TP53 mutation breast cancer immunocytes infiltration prognosis Biology (General) QH301-705.5
spellingShingle	TP53 mutation breast cancer immunocytes infiltration prognosis Biology (General) QH301-705.5 Ziwen Zhang Ziwen Zhang Ran Hao Qiusheng Guo Qiusheng Guo Sheyu Zhang Xiaojia Wang Xiaojia Wang TP53 Mutation Infers a Poor Prognosis and Is Correlated to Immunocytes Infiltration in Breast Cancer
description	Background: This study aimed to investigate the TP53 mutation, its potential immune features, its prognostic value, and its impact on immune infiltration in patients with breast cancer (BC).Methods: We downloaded the somatic mutation data and clinicopathologic features of BC patients from the TCGA GDC database, UCSC Xena platform, and International Cancer Genome Consortium (ICGC) database. The association between the TP53 mutation, clinicopathology features, and overall survival (OS) in BC patients was analyzed. We evaluated the potential role of the TP53 mutation in the immune therapy response, including the tumor mutation burden (TMB), microsatellite instability (MSI), and tumor immune dysfunction and exclusion (TIDE). Moreover, ESTIMATE was employed to assess the ImmuneScore and StromalScore in BC patients. We also explored immunocyte infiltration related to the TP53 mutation and its potential mechanism. Immunohistochemistry (IHC) was performed to validate the association between the expression of CXCL1, CXCL10, and CCL20 and TP53 status.Results: We found that the TP53 mutation was significantly associated with the shorter OS (p = 0.038) and was also an independent predictive factor of OS for BC patients (p < 0.001). Compared to that in the wild type group, the TP53-mutant group showed a higher TMB value (P< 0.001), MSI value (p = 0.077), and TIDE value (p < 0.001) with respect to BC patient immunotherapy. In addition, the ImmuneScore and StromalScore were both significantly increased in the TP53-mutant group (ImmuneScore: p < 0.001; StromalScore: p = 0.003). The results of CIBERSORT suggested that the TP53 mutation significantly promoted the infiltration of Tregs, T helper cells, and M0-type macrophages. KEGG and GSEA enrichment results suggested that the IL-17 signaling pathway and antigen processing and presentation pathways were significantly enriched in the TP53-mutant group. Importantly, based on IHC results of immune-related hub-genes, the chemokines CXCL1, CXCL10, and CCL20 were significantly upregulated in the TP53-mutant group in BC patients.Conclusion: These results indicate that a TP53 mutation might serve as a biomarker for BC prognosis and is related to immunocyte infiltration in the tumor microenvironment.
format	article
author	Ziwen Zhang Ziwen Zhang Ran Hao Qiusheng Guo Qiusheng Guo Sheyu Zhang Xiaojia Wang Xiaojia Wang
author_facet	Ziwen Zhang Ziwen Zhang Ran Hao Qiusheng Guo Qiusheng Guo Sheyu Zhang Xiaojia Wang Xiaojia Wang
author_sort	Ziwen Zhang
title	TP53 Mutation Infers a Poor Prognosis and Is Correlated to Immunocytes Infiltration in Breast Cancer
title_short	TP53 Mutation Infers a Poor Prognosis and Is Correlated to Immunocytes Infiltration in Breast Cancer
title_full	TP53 Mutation Infers a Poor Prognosis and Is Correlated to Immunocytes Infiltration in Breast Cancer
title_fullStr	TP53 Mutation Infers a Poor Prognosis and Is Correlated to Immunocytes Infiltration in Breast Cancer
title_full_unstemmed	TP53 Mutation Infers a Poor Prognosis and Is Correlated to Immunocytes Infiltration in Breast Cancer
title_sort	tp53 mutation infers a poor prognosis and is correlated to immunocytes infiltration in breast cancer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/a5c845d4d34046febd184ba468ac3854
work_keys_str_mv	AT ziwenzhang tp53mutationinfersapoorprognosisandiscorrelatedtoimmunocytesinfiltrationinbreastcancer AT ziwenzhang tp53mutationinfersapoorprognosisandiscorrelatedtoimmunocytesinfiltrationinbreastcancer AT ranhao tp53mutationinfersapoorprognosisandiscorrelatedtoimmunocytesinfiltrationinbreastcancer AT qiushengguo tp53mutationinfersapoorprognosisandiscorrelatedtoimmunocytesinfiltrationinbreastcancer AT qiushengguo tp53mutationinfersapoorprognosisandiscorrelatedtoimmunocytesinfiltrationinbreastcancer AT sheyuzhang tp53mutationinfersapoorprognosisandiscorrelatedtoimmunocytesinfiltrationinbreastcancer AT xiaojiawang tp53mutationinfersapoorprognosisandiscorrelatedtoimmunocytesinfiltrationinbreastcancer AT xiaojiawang tp53mutationinfersapoorprognosisandiscorrelatedtoimmunocytesinfiltrationinbreastcancer
_version_	1718404710713524224

TP53 Mutation Infers a Poor Prognosis and Is Correlated to Immunocytes Infiltration in Breast Cancer

Ejemplares similares