The tumor-suppressive role of BATF2 in esophageal squamous cell carcinoma

BATF2 has been found to be decreased in a variety of human malignancies, while its clinical significance and functional roles in esophageal squamous cell carcinoma (ESCC) remain unknown. Herein, the aim of this study was to investigate the expression pattern and to explore the potential functions of BATF2 in ESCC tissues and cell lines. BATF2 mRNA and protein expression levels in human tissues and human ESCC cell lines were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting (WB) and immunohistochemical (IHC) analyses. BATF2 was upregulated by transfection of the pcDNA3.1-BATF2 plasmid into KYSE-410 cells. MTT and Transwell assays were used to investigate the effects of BATF2 on cellular proliferation and invasion. Survival curves were plotted using Kaplan-Meier plots and log-rank tests. Cox's proportional hazards regression model was used to analyze univariate and multivariate survival. The results showed that, compared to the matched non-tumor tissues from 36 ESCC patients, 80.56% (29/36) of the tumor tissues presented downregulation of BATF2 by WB analysis (P<0.001). The results of IHC in 104 patients who underwent surgery for ESCC showed that the expression of BATF2 was closely related to tumor differentiation (P=0.023) and lymph node metastasis (P=0.027), while there was no significant correlation with age (P=0.574), gender (P=0.357), tumor location (P=0.721) and TNM stage (P=0.126) of the patients. Pathological grade (P=0.027), clinical stage (P=0.000), lymph node metastasis (P=0.002) and BATF2 expression (P=0.028) were identified as independent prognostic factors for overall survival (OS). In the in vitro studies, upregulation of BATF2 expression significantly inhibited the proliferation and invasive ability of the human ESCC KYSE-410 cells. In conclusion, as a tumor suppressor, BATF2 serves as a prognostic biomarker of ESCC and it may be a potential therapeutic target for ESCC treatment.