In:
PLOS ONE, Public Library of Science (PLoS), Vol. 18, No. 8 ( 2023-8-16), p. e0289960-
Abstract:
Patients with systemic lupus erythematosus (SLE) have a lower risk of breast cancer (BRCA) than the general population. In this study, we explored the underlying molecular mechanism that is dysregulated in both diseases. Methods Weighted gene coexpression network analysis (WGCNA) was executed with the SLE and BRCA datasets from the Gene Expression Omnibus (GEO) website and identified the potential role of membrane metalloendopeptidase (MME) in both diseases. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of related proteins and miRNAs were performed to investigate the potential molecular pathways. Results WGCNA revealed that MME was positively related to SLE but negatively related to BRCA. In BRCA, MME expression was significantly decreased in tumor tissues, especially in luminal B and infiltrating ductal carcinoma subtypes. Receiver operating characteristic (ROC) analysis identified MME as a valuable diagnostic biomarker of BRCA, with an area under the curve (AUC) value equal to 0.984 (95% confidence interval = 0.976–0.992). KEGG enrichment analysis suggested that MME-related proteins and targeted miRNAs may reduce the incidence of BRCA in SLE patients via the PI3K/AKT/FOXO signaling pathway. Low MME expression was associated with favorable relapse-free survival (RFS) but no other clinical outcomes and may contribute to resistance to chemotherapy in BRCA, with an AUC equal to 0.527 (P value 〈 0.05). Conclusions In summary, MME expression was significantly decreased in BRCA but positively correlated with SLE, and it might reduce the incidence of BRCA in SLE patients via the PI3K/AKT/FOXO signaling pathway.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0289960
DOI:
10.1371/journal.pone.0289960.g001
DOI:
10.1371/journal.pone.0289960.g002
DOI:
10.1371/journal.pone.0289960.g003
DOI:
10.1371/journal.pone.0289960.g004
DOI:
10.1371/journal.pone.0289960.t001
DOI:
10.1371/journal.pone.0289960.s001
DOI:
10.1371/journal.pone.0289960.s002
DOI:
10.1371/journal.pone.0289960.s003
DOI:
10.1371/journal.pone.0289960.s004
DOI:
10.1371/journal.pone.0289960.s005
DOI:
10.1371/journal.pone.0289960.s006
DOI:
10.1371/journal.pone.0289960.s007
DOI:
10.1371/journal.pone.0289960.s008
DOI:
10.1371/journal.pone.0289960.s009
DOI:
10.1371/journal.pone.0289960.s010
DOI:
10.1371/journal.pone.0289960.r001
DOI:
10.1371/journal.pone.0289960.r002
DOI:
10.1371/journal.pone.0289960.r003
DOI:
10.1371/journal.pone.0289960.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2267670-3
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