Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine.
Breast cancer (BC) is a malignancy with high incidence among women in the world. This study aims to screen key genes and potential prognostic biomarkers for BC using bioinformatics analysis. Total 58 normal tissues and 203 cancer tissues were collected from three Gene Expression Omnibus (GEO) gene expression profiles, and then the differential expressed genes (DEGs) were identified. Subsequently, the Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway were analyzed to investigate the biological function of DEGs. Additionally, hub genes were screened by constructing a protein-protein interaction (PPI) network. Then, we explored the prognostic value and molecular mechanism of these hub genes using Kaplan-Meier (KM) curve and Gene Set Enrichment Analysis (GSEA). As a result, 42 upregulated and 82 down-regulated DEGs were screened out from GEO datasets. The DEGs were mainly related to cell cycles and cell proliferation by GO and KEGG pathway analysis. Furthermore, 12 hub genes (FN1,
Objective
Although T-cell immunoglobulin and mucin-domain containing molecule-3 (Tim-3) has been recognized as a promising target for cancer immunotherapy, its exact role in breast cancer has not been fully elucidated.
Methods
Tim-3
gene expression in breast cancer and its prognostic significance were analyzed. Associated mechanisms were then explored
in vitro
by establishing Tim-3-overexpressing breast cancer cells.
Results
In a pooled analysis of The Cancer Genome Atlas (TCGA) database,
Tim-3
gene expression levels were significantly higher (P<0.001) in breast cancer tissue, compared with normal tissues. Tim-3 was a prognosis indicator in breast cancer patients [relapse-free survival (RFS), P=0.004; overall survival (OS), P=0.099]. Tim-3 overexpression in Tim-3
low
breast cancer cells promoted aggressiveness of breast cancer cells, as evidenced by enhanced proliferation, migration, invasion, tight junction deterioration and tumor-associated tubal formation. Tim-3 also enhanced cellular resistance to paclitaxel. Furthermore, Tim-3 exerted its function by activating the NF-κB/STAT3 signalling pathway and by regulating gene expression [cyclin D1 (
CCND1
),
C-Myc
, matrix metalloproteinase-1(
MMP1
),
TWIST
, vascular endothelial growth factor (
VEGF
) upregulation, concomitant with
E-cadherin
downregulation). Lastly, Tim-3 downregulated tight junction-associated molecules zona occludens (ZO)-2, ZO-1 and occludin, which may further facilitate tumor progression.
Conclusions
Tim-3 plays an oncogenic role in breast cancer and may represent a potential target for antitumor therapy.
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