Abstract. Decreased expression of human chemokine-like factor-like MARVEL transmembrane domain-containing 3 (CMTM3) has been identified in a number of human tumors and tumor cell lines, including gastric and testicular cancer, and PC3, CAL27 and Tca-83 cell lines. However, the association between CMTM3 expression and the clinicopathological features and prognosis of esophageal squamous cell carcinoma (ESCC) patients remains unclear. The aim of the present study was to investigate the correlation between CMTM3 expression and clinicopathological parameters and prognosis in ESCC. CMTM3 mRNA and protein expression was analyzed in ESCC and paired non-tumor tissues by quantitative real-time polymerase chain reaction, western blotting and immunohistochemical analysis. The Kaplan-Meier method was used to plot survival curves and the Cox proportional hazards regression model was also used for univariate and multivariate survival analysis. The results revealed that CMTM3 mRNA and protein expression levels were lower in 82.5% (30/40) and 75% (30/40) of ESCC tissues, respectively, when compared with matched non-tumor tissues. Statistical analysis demonstrated that CMTM3 expression was significantly correlated with lymph node metastasis (P=0.002) and clinical stage (P<0.001) in ESCC tissues. Furthermore, the survival time of ESCC patients exhibiting low CMTM3 expression was significantly shorter than that of ESCC patients exhibiting high CMTM3 expression (P=0.01). In addition, Kaplan-Meier survival analysis revealed that the overall survival time of patients exhibiting low CMTM3 expression was significantly decreased compared with patients exhibiting high CMTM3 expression (P=0.010). Cox multivariate analysis indicated that CMTM3 protein expression was an independent prognostic predictor for ESCC after resection. This study indicated that CMTM3 expression is significantly decreased in ESCC tissues and CMTM3 protein expression in resected tumors may present an effective prognostic biomarker.

Abstract. 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.