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High TNFRSF12A level associated with MMP-9 overexpression is linked to poor prognosis in breast cancer: Gene set enrichment analysis and validation in large-scale cohorts

Title
High TNFRSF12A level associated with MMP-9 overexpression is linked to poor prognosis in breast cancer: Gene set enrichment analysis and validation in large-scale cohorts
Author
민경환
Keywords
MATRIX-METALLOPROTEINASE-9 MMP-9; MATRIX METALLOPROTEINASES; EXPRESSION; CARCINOMA; ANGIOGENESIS; PROGRESSION; INVASION; COLLAGEN; CELLS
Issue Date
2018-08
Publisher
PUBLIC LIBRARY SCIENCE
Citation
PLOS ONE, v. 13, no. 8, Article no. e0202113
Abstract
BackgroundMatrix metalloproteinase-9 (MMP-9) is associated with remodelling of the extracellular matrix and invasion in various cancers. Identifying proteins connected to high MMP-9 expression is important in explaining its mechanisms. Our study aims to shed light on genes associated with high MMP-9 expression and to discuss their clinical impact in breast cancer.MethodsWe evaluated 173 breast cancer cases from the Kangbuk Samsung Hospital, with 1964 cases from the Molecular Taxonomy of Breast Cancer International Consortium database serving as a validation cohort. We investigated relationships between MMP-9 expression and clinicopathological characteristics. We then used gene set enrichment analyses to detect the association of genes with MMP-9 overexpression, and performed survival analyses to determine the significance of the gene in three independent cohorts.ResultsHigh MMP-9 expression correlated with poor prognosis in univariate and multivariate analyses. Using gene set enrichment analysis, we found that tumour necrosis factor receptor superfamily member 12A (TNFRSF12A) was linked to high MMP-9 expression. In the survival analysis of three published data sets (METABRIC, GSE1456, GSE20685), high TNFRSF12A was relevant to a poor survival rate.ConclusionsHigh levels of TNFRSF12A associated with MMP-9 overexpression may be important to explain the progression of breast cancer, and survival could be improved using therapy targeting TNFRSF12A.
URI
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0202113http://repository.hanyang.ac.kr/handle/20.500.11754/119659
ISSN
1932-6203
DOI
10.1371/journal.pone.0202113
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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