Affiliation:
1. Department of thoracic surgery, Chaohu Hospital affiliated with Anhui Medical University, Hefei, 238000, China
Abstract
Background:
Bridging integrator 3 (BIN3) has been reported to play a key role in certain
tumors. Nevertheless, little is known about the role and clinical value of BIN3 in esophagus
carcinoma (ESCA). This study aimed to investigate the pathological and prognostic role of BIN3
in ESCA patients.
Methods:
Genes significantly correlated with the prognosis of ESCA patients were screened and
identified by comprehensive analysis of differentially expressed genes associated with overall survival
(OS), disease-specific survival (DSS) and progression-free interval (PFI) in ESCA. The expression
of BIN3, pathological features correlation and subgroup overall survival analysis were
performed using The Cancer Genome Atlas (TCGA) and GTEx databases. Moreover, the potential
signaling pathways in which BIN3 was involved were analyzed by GO-KEGG enrichment analysis
and gene set enrichment analysis (GSEA). Immune infiltrates correlation of BIN3 in ESCA was
performed by TIMER and ssGSEA. The influence of BIN3 on epithelial-mesenchymal transition
(EMT) was validated by western blot.
Results:
There were two differentially expressed genes related to the prognosis of ESCA patients,
which were identified from three gene clusters associated with overall survival (OS), diseasespecific
survival (DSS) and progression-free interval (PFI) in ESCA patients. The BIN3 mRNA
level was found to be significantly decreased in ESCA compared to normal tissues (p < 0.05). The
decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p =
0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05).
ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4),
age (<=60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable
OS. GO-KEGG enrichment analysis revealed that BIN3 was involved in endocytosis.
GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of
mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome
regulation of beta cell development, WP Urea cycle and associated pathways and others. BIN3 was
significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p <
0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). In addition, BIN3 overexpression
inhibited N-cadherin expression and promoted E-cadherin expression in ESCA cell lines TE-1.
Conclusion:
These results suggest that BIN3 might be a potential prognostic biomarker in ESCA.
BIN3 functions as a tumor-suppressor role in ESCA, which is significantly associated with the
immune infiltration of ESCA.
Publisher
Bentham Science Publishers Ltd.
Subject
Organic Chemistry,Computer Science Applications,Drug Discovery,General Medicine
Cited by
1 articles.
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