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The tumor-suppressive role of BATF2 in esophageal squamous cell carcinoma
Tianci Han1, Zhiyong Wang1, Yang Yang2
1Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
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.
Insights
The study found that BATF2 is downregulated in esophageal squamous cell carcinoma (ESCC) and acts as a tumor suppressor. Upregulating BATF2 inhibits ESCC cell proliferation and invasion, identifying it as a prognostic biomarker and potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- BATF2 (Basic Leucine Zipper Transcription Factor Subunit 2) expression is reduced in various human cancers.
- The role and clinical significance of BATF2 in esophageal squamous cell carcinoma (ESCC) are not well understood.
Purpose of the Study:
- To investigate the expression pattern of BATF2 in ESCC tissues and cell lines.
- To explore the functional roles of BATF2 in ESCC.
- To evaluate BATF2 as a potential prognostic biomarker and therapeutic target for ESCC.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR), western blotting (WB), and immunohistochemical (IHC) analyses were used to assess BATF2 expression.
- In vitro assays (MTT, Transwell) were performed to evaluate the effects of BATF2 on cell proliferation and invasion.
- Survival analysis utilized Kaplan-Meier plots, log-rank tests, and Cox's proportional hazards regression model.
Main Results:
- BATF2 was significantly downregulated in 80.56% of ESCC tumor tissues compared to matched non-tumor tissues.
- BATF2 expression correlated with tumor differentiation and lymph node metastasis but not age, gender, tumor location, or TNM stage.
- BATF2 downregulation, pathological grade, clinical stage, and lymph node metastasis were identified as independent prognostic factors for overall survival (OS).
- Upregulation of BATF2 in vitro suppressed ESCC cell proliferation and invasion.
Conclusions:
- BATF2 functions as a tumor suppressor in ESCC.
- BATF2 is a valuable prognostic biomarker for ESCC.
- BATF2 represents a potential therapeutic target for ESCC treatment.
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