Decreased expression of BATF2 is significantly associated with poor prognosis in oral tongue squamous cell carcinoma.
Decreased expression of BATF2 is significantly associated with poor prognosis in oral tongue squamous cell carcinoma.
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DOI：
10.3892/or.2013.2863
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发表时间：
2014
期刊：
影响因子：
4.2
通讯作者：
Haojie Wen;Yajun Chen;Zedong Hu;Qiao Mo;Jinyong Tang;Chuanzheng Sun
中科院分区：
文献类型：
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作者：
Haojie Wen;Yajun Chen;Zedong Hu;Qiao Mo;Jinyong Tang;Chuanzheng Sun
BATF2，也称为SARI，与几种癌症类型相关，并且在侵袭性和转移性癌症中经常检测到BATF2表达的缺失。BATF2的表达以前被证明可以减缓注射到无胸腺裸鼠中的恶性肿瘤细胞的生长速率，并且BATF2的表达降低与肝细胞癌的不良预后相关。然而，BATF2在口腔舌鳞状细胞癌（OTSCC）中的功能作用仍然未知。在本研究中，我们研究了BATF2的表达在16个新鲜的，成对的OTSCC和邻近的非肿瘤组织，以及在正常的舌上皮细胞系和5 OTSCC细胞系的定量PCR和蛋白质印迹分析。我们还通过免疫组织化学方法评估了202例石蜡包埋的OTSCC和30例邻近非肿瘤样本中BATF2的表达，并研究了其与临床病理特征和预后的关系。我们发现，当分别与非肿瘤组织和正常舌上皮细胞系相比时，BATF2表达在16个OTSCC肿瘤组织和5个OTSCC细胞系中的大多数中显著降低。与这些结果一致，我们的免疫组化分析显示，202例病例中有124例存在BATF2表达降低，并且与肿瘤分化不良显著相关（P=0.002）。与高表达患者相比，BATF2表达降低的患者生存率降低（P<0.001）。多变量分析显示，BATF2表达是总生存率的独立预测因子（P=0.001）。这些结果表明，BATF 2在OTSCC的发展中发挥肿瘤抑制作用，并且BATF 2可能作为该疾病的预后生物标志物和潜在治疗靶点。
BATF2, also called SARI, is associated with several cancer types, and loss of BATF2 expression is frequently detected in aggressive and metastatic cancers. The expression of BATF2 was previously shown to slow the growth rate of malignant tumor cells injected into athymic nude mice, and decreased expression of BATF2 has been correlated to poor prognosis in hepatocellular carcinoma. However, the functional role of BATF2 in oral tongue squamous cell carcinoma (OTSCC) remains unknown. In the present study, we examined BATF2 expression in 16 fresh, paired OTSCC and adjacent non-tumor tissues, as well as in a normal tongue epithelial cell line and in 5 OTSCC cell lines by quantitative PCR and western blot analysis. We also evaluated BATF2 expression in 202 paraffin‑embedded OTSCC and 30 adjacent non-tumor samples by immunohistochemistry, and its relationship with clinicopathological features and prognosis was investigated. We found that BATF2 expression was significantly reduced in the majority of the 16 OTSCC tumor tissues and the 5 OTSCC cell lines when compared with the non-tumor tissues and the normal tongue epithelial cell line, respectively. Consistent with these results, our immunohistochemistry analysis revealed that decreased BATF2 expression was present in 124 of the 202 cases and was significantly correlated with poor tumor differentiation (P=0.002). Patients with decreased BATF2 expression showed reduced survival when compared to those with high expression (P<0.001). Multivariate analysis revealed that BATF2 expression is an independent predictor of overall survival (P=0.001). These results demonstrate that BATF2 plays a tumor-suppressor role in the development of OTSCC and that BATF2 may serve as a prognostic biomarker and potential therapeutic target for this disease.