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

doi:10.3389/fcell.2021.759154

	TP53 Mutation Infers a Poor Prognosis and Is Correlated to Immunocytes Infiltration in Breast Cancer
	Zhang, Ziwen 2,4; Hao, Ran 5; Guo, Qiusheng 2,3; Zhang, Sheyu 1; Wang, Xiaojia 2,4
刊名	FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
	2021-11-30
卷号	9
关键词	TP53 mutation breast cancer immunocytes infiltration prognosis
ISSN号	2296-634X
DOI	10.3389/fcell.2021.759154
通讯作者	Wang, Xiaojia(wxiaojia0803@163.com)
英文摘要	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.
资助项目	Hebei Key Research and Development Project[19277799D] ; Hebei Key Research and Development Project[21377729D] ; Natural Science Foundation of Hebei Province[H2020206483] ; Natural Science Foundation of Hebei Province[H2021206289]
WOS关键词	GENE ; P53
WOS研究方向	Cell Biology ; Developmental Biology
语种	英语
出版者	FRONTIERS MEDIA SA
WOS记录号	WOS:000729924600001
资助机构	Hebei Key Research and Development Project ; Natural Science Foundation of Hebei Province
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/126470]
专题	中国科学院合肥物质科学研究院
通讯作者	Wang, Xiaojia
作者单位	1.Tianjin Univ, Sch Pharmaceut Sci & Technol, Tianjin, Peoples R China 2.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Med Oncol Breast Canc, Hangzhou, Peoples R China 3.Zhejiang Chinese Med Univ, Clin Coll 2, Hangzhou, Peoples R China 4.Chinese Acad Sci, Inst Canc & Basic Med, Hangzhou, Peoples R China 5.Hebei Med Univ, Sch Nursing, Shijiazhuang, Hebei, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Ziwen,Hao, Ran,Guo, Qiusheng,et al. TP53 Mutation Infers a Poor Prognosis and Is Correlated to Immunocytes Infiltration in Breast Cancer[J]. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,2021,9.
APA	Zhang, Ziwen,Hao, Ran,Guo, Qiusheng,Zhang, Sheyu,&Wang, Xiaojia.(2021).TP53 Mutation Infers a Poor Prognosis and Is Correlated to Immunocytes Infiltration in Breast Cancer.FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,9.
MLA	Zhang, Ziwen,et al."TP53 Mutation Infers a Poor Prognosis and Is Correlated to Immunocytes Infiltration in Breast Cancer".FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 9(2021).