Aberrant expression of EZH2 is associated with a poor outcome and P53 alteration in squamous cell carcinoma of the esophagus
Aberrant expression of EZH2 is associated with a poor outcome and P53 alteration in squamous cell carcinoma of the esophagus
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DOI：
10.3892/ijo.2010.868
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发表时间：
2011-02-01
影响因子：
5.2
通讯作者：
Ochiai, Atsushi
中科院分区：
文献类型：
--
作者：
Yamada, Atsushi;Fujii, Satoshi;Ochiai, Atsushi
EZH2和BMI1是转录抑制因子，与人类癌症的进展有关。食道鳞状细胞癌(ESCC)是胃肠道最具侵袭性的肿瘤之一，一般预后不佳。在本研究中，我们用免疫组织化学方法检测了136例手术切除的食管鳞癌及癌旁上皮中EZH2和BMI1的表达。我们还分析了EZH2和BMI1的异常表达与临床病理结果和预后的关系。在选定的病例中检测MYC、Rb和P53的表达，并分析其与EZH2表达的关系。用直接测序法检测p53基因的突变情况。研究EZH2mRNA在具有和不具有P53转录活性的ESCC细胞系中的表达。结果表明，EZH2和BMI1蛋白在食管鳞癌组织中的表达高于癌旁非肿瘤性上皮组织。EZH2和BMI1蛋白在136例食管癌中的异常表达分别为19例(14.0%)和23例(16.9%)。EZH2的异常表达与肿瘤的大小、侵袭深度、远处转移和较短的无瘤生存期显著相关。BMI1的异常表达与患者的淋巴结转移和静脉侵犯呈负相关，但与患者的生存无关。此外，食管鳞癌组织中EZH2的异常表达与P53的改变有关。P53的激活降低了EZH2mRNA的表达。结论：EZH2基因异常表达可能与P53基因改变有关，EZH2基因异常表达可能在ESCC的发生发展中起一定作用。
EZH2 and BMI1 are transcriptional repressors and have been implicated in the progression of human cancers. Squamous cell carcinoma of the esophagus (ESCC) is one of the most aggressive carcinomas in the gastrointestinal tract and generally has an unfavorable outcome. In the present study, we immunohistochemically investigated the expression of EZH2 and BMI1 in 136 surgically resected ESCCs and adjacent epithelium. We also analyzed associations between aberrant expression of EZH2 and BMI1, and both clinicopathological findings and outcome. MYC, RB, and P53 expression was examined in selected cases and analyzed in relation to EZH2 expression. Mutations in the P53 gene were evaluated by direct sequencing. EZH2 mRNA expression was investigated in ESCC cell lines with and without P53 transcriptional activity. The results showed that EZH2 protein and BMI1 protein were upregulated in ESCC tissue in comparison with adjacent non-neoplastic epithelium. Aberrant EZH2 and BMI1 protein expression was observed in 19 (14.0%) and 23 (16.9%), respectively, of the 136 ESCCs. Aberrant EZH2 expression was significantly associated with larger size, greater depth of invasion, presence of distant metastasis, and shorter disease-free survival time. Aberrant BMI1 expression was inversely associated with lymph node metastasis and venous invasion, but not associated with survival of the patients. In addition, aberrant EZH2 expression was associated with P53 alteration in ESCC tissue. EZH2 mRNA expression in ESCC cell lines was reduced by activation of P53. In conclusion, P53 alteration may be involved in dysregulated EZH2 expression, and aberrant expression of EZH2 may play a role in ESCC progression.