Low expression of BEX1 predicts poor prognosis in patients with esophageal squamous cell cancer

Abstract

The brain expressed x‑linked gene 1 (BEX1) is a member of the BEX family and is aberrantly expressed in many cancers. However, the clinical significance of BEX1 expression level and its role in the pathology of esophageal squamous cell cancer (ESCC) remain unknown. In the present study, we determined BEX1 expression in the tumor and adjacent normal tissues from 118 ESCC patients by immunohistochemistry and determined the proliferation and growth of ESCC cells following ectopic overexpression of BEX1 in cultured cells and in mouse‑ESCC xenografts. We observed that BEX1 was downregulated in ESCC tissues compared to adjacent normal tissues, and low BEX1 expression was significantly associated with larger ESCC tumor volume (P<0.001), advanced T stage (P=0.011) and advanced clinical stage (P=0.039). Additionally, survival analysis revealed that low expression of BEX1 significantly predicted poor prognosis in patients with ESCC (P<0.001). Multivariate analysis revealed that low BEX1 expression was an independent prognostic factor of poor survival (P=0.039). In vitro analysis revealed that overexpression of BEX1 inhibited ESCC cell proliferation and colony formation. Furthermore, in vivo tumorigenesis assays revealed that ectopic overexpression of BEX1 suppressed ESCC tumor growth in mice. Further immunoblotting analysis demonstrated that BEX1 upregulation led to reduced expression and phosphorylation of NF‑κB p65, indicating inhibition of the NF‑κB signaling pathway by BEX1. Our findings indicated that low BEX1 expression may be an independent prognostic marker for poor survival and may serve as a potential target for ESCC therapy.

An R package for divergence analysis of omics data

“…Regulator of G protein signaling 6 (RGS6), which is down-divergent in most tumor samples, has been observed to be a suppressor of breast cancer [19]. BEX1 has been linked to ER+ breast cancer (a greater proportion of ER+ samples are divergent compared to ER− samples), as well as acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and squamous cell cancer [20–22]. The human protein atlas data suggests PROZ as a prognostic marker in liver cancer, with higher protein expression observed in a subset of breast cancer samples [23, 24].…”

Long Noncoding RNA LINC00526 Represses Glioma Progression via Regulating miR-5581-3p/BEX1

“…Subsequently, BEX1 was confirmed as a target of miR-5581-3p in glioma. BEX1 belongs to the BEX family and is found abnormally expressed in cancers [13][14][15]. For example, low BEX1 was identified in esophageal squamous cell cancer and significantly correlated with large tumor size and late tumor stage [13].…”

Diagnostic and prognostic value of the BEX family in lung adenocarcinoma

“…Therefore, novel biomarkers for the detection and prognosis evaluation of LUAD are required. Previous studies have revealed that the BEX family may serve roles as predictive biomarkers in tumors, such as esophageal squamous cell cancer and acute myeloid leukemia (12,40). The potential clinical value of the BEX family members in LUAD warrants further research.…”

“…A previous study reported that low expression of BEX1 was associated with clinicopathological characteristics such as tumor volume, T stage and clinical stage in esophageal squamous cell cancer (12). The present study investigated the association between the expression of the BEX family and the clinicopathological features of patients with LUAD.…”

“…BEX1 is implicated in leukemogenesis, and aberrant downregulation of BEX1 has been observed in acute and chronic myeloid leukemia (10,11). Furthermore, BEX1 is associated with the development of other types of cancer, including pediatric intracranial ependymoma and esophageal squamous cell cancer (12,13). BEX2 may serve as an oncogene in different types of cancer, including glioma, breast and colorectal cancer (14–16).…”