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Landscape Analysis of Matrix Metalloproteinases Unveils Key Prognostic Markers for Patients With Breast Cancer
Cheng, Tianyi1; Chen, Peiying1; Chen, Jingyi1; Deng, Yingtong1; Huang, Chen1,2
2022-01-06
Source PublicationFrontiers in Genetics
ISSN1664-8021
Volume12
Abstract

Breast cancer (BRCA) is the most common cancer in the world, of which incidence rate and mortality are the highest in women. Being responsible for the remodeling and degradation of extracellular matrix proteins, matrix metalloproteinases (MMPs) have been regarded as one of the most important protease family related to tumorigenesis. It has been demonstrated that MMPs play crucial roles in some tumor invasion and metastasis. However, the potential roles of MMPs in tumorigenesis and progression of BRCA and its subtype remain elusive. Herein, we conducted a systematic study on MMPs via a series of database-based retrospective analysis, including TCGA, R Studio, GEPIA, Kaplan-Meier Plotter, cBioPortal, STRING, GeneMANIA and TIMER. As a result, many MMP family members were differentially expressed in patients with BRCA, e.g., the expressions of MMP1, MMP9, MMP11 and MMP13 were up-regulated, whereas the expression levels of MMP19 and MMP28 were down-regulated. MMP9, MMP12, MMP15 and MMP27 were significantly correlated with the clinical stages of BRCA, implying their important roles in the occurrence and development of BRCA. In addition, the survival analysis indicated that different expression pattern of MMPs exhibited distinct outcomes in patient with BRCA, e.g., patients with high expression of MMP2, MMP8, MMP16, MMP17, MMP19, MMP20, MMP21, MMP24, MMP25, MMP26 and MMP27 had a prolonged survival time, while the others (MMP1, MMP7, MMP9, MMP12 and MMP15) exhibited poor prognosis. Subsequent functional and network analysis revealed MMPs were mainly correlated with parathyroid hormone synthesis and secretion pathway, collagen metabolism, and their effect on the activities of serine hydrolase, serine peptidase and aminopeptidase. Notably, our analysis showed that the expression of MMPs was significantly correlated with the infiltration of various immune cells in BRCA, including CD8+T cells, CD4+T cells, macrophages, neutrophils, B cells, and dendritic cells, suggesting the close correlations between MMPs and immune functions. In short, our study disclosed MMPs play multiple biological roles in the development of BRCA, MMP1 and MMP9 might be used as independent prognostic markers and potential therapeutic targets for diagnosis and treatment for patients with BRCA.

KeywordBioinformatics Breast Cancer Immune Infiltration Matrix Metalloproteinases Prognostic Value
DOI10.3389/fgene.2021.809600
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaGenetics & Heredity
WOS SubjectGenetics & Heredity
WOS IDWOS:000745843800001
PublisherFRONTIERS MEDIA SA, AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE CH-1015, SWITZERLAND
Scopus ID2-s2.0-85123179023
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Citation statistics
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorHuang, Chen
Affiliation1.Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macao
2.Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology, Macao
First Author AffilicationUniversity of Macau
Corresponding Author AffilicationUniversity of Macau
Recommended Citation
GB/T 7714
Cheng, Tianyi,Chen, Peiying,Chen, Jingyi,et al. Landscape Analysis of Matrix Metalloproteinases Unveils Key Prognostic Markers for Patients With Breast Cancer[J]. Frontiers in Genetics, 2022, 12.
APA Cheng, Tianyi., Chen, Peiying., Chen, Jingyi., Deng, Yingtong., & Huang, Chen (2022). Landscape Analysis of Matrix Metalloproteinases Unveils Key Prognostic Markers for Patients With Breast Cancer. Frontiers in Genetics, 12.
MLA Cheng, Tianyi,et al."Landscape Analysis of Matrix Metalloproteinases Unveils Key Prognostic Markers for Patients With Breast Cancer".Frontiers in Genetics 12(2022).
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