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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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景已报道桥接整合因子3(BIN3)在某些肿瘤中起关键作用。然而，关于BIN3在食管癌（ESCA）中的作用和临床价值知之甚少。本研究旨在探讨BIN3在ESCA患者中的病理和预后作用。方法综合分析ESCA患者的总生存期(OS)差异表达基因,筛选并鉴定与预后显著相关的基因。ESCA的疾病特异性生存期（DSS）和无进展间期（PFI）。使用癌症基因组图谱（TCGA）和GTEx数据库进行BIN3的表达，病理特征相关性和亚组总体生存分析。此外，通过GO-KEGG富集分析和基因集富集分析(GSEA)分析BIN3参与的潜在信号通路.通过TIMER和ssGSEA进行ESCA中BIN3的免疫浸润相关性。通过westernblot验证BIN3对上皮间质转化（EMT）的影响。结果ESCA患者存在两个与预后相关的差异表达基因,从与总生存期（OS）相关的三个基因簇中鉴定出，ESCA患者的疾病特异性生存期（DSS）和无进展间期（PFI）。发现与正常组织相比,ESCA中的BIN3mRNA水平显著降低(p<0.05)。ESCA中BIN3的表达降低与临床分期显著相关(p=0.015),T分期(p<0.05)，组织学类型（p<0.001），年龄(p<0.05)和性别(p<0.05)。观察到具有高BIN3表达的ESCA患者与T分期（T3和T4）相关，年龄（＜＝60），性别（男性），主要治疗结果（PD）和柱状化生（无）的有利OS。GO-KEGG富集分析显示BIN3参与胞吞作用。GSEA表明，BIN3中富集了几种途径，例如粘蛋白的O连接糖基化，PIDHNF3B通路，BiocartaTFF途径，WP孕烷X受体通路，β细胞发育的反应体调节，WP尿素循环和相关途径等。BIN3与T细胞浸润水平显著相关(p<0.001),Tregs（p<0.001），B细胞（p<0.001），NK细胞（p<0.001），和巨噬细胞M2(p<0.001)。此外,在ESCA细胞系TE-1中,BIN3过表达抑制N-cadherin表达并促进E-cadherin表达。结论这些结果表明BIN3可能是ESCA的潜在预后生物标志物。BIN3在ESCA中起肿瘤抑制作用，与ESCA的免疫浸润密切相关。
