Matsukawa Yasuko, Semba Shuho, Kato Hirotaka, Ito Akihiko, Yanagihara Kazuyoshi, Yokozaki Hiroshi
Division of Surgical Pathology, Department of Biomedical Informatics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Cancer Sci. 2006 Jun;97(6):484-91. doi: 10.1111/j.1349-7006.2006.00203.x.
Overexpression of the enhancer of zeste homolog 2 (EZH2) protein, a known repressor of gene transcription, has been reported to be associated with biological malignancy of prostate cancer and several other cancers. The purpose of this study was to examine the expression of EZH2 and analyze its relationship with the clinicopathological features of human gastric cancers. Expression levels of EZH2 mRNA and protein were examined in 13 gastric cancer cell lines and in 83 surgically removed human gastric cancer tissues. Immunohistochemical analysis of the 83 tissue samples and corresponding non-cancerous gastric mucosa showed that EZH2 was more highly expressed in the cancerous than in the non-cancerous tissues, and the expression levels of EZH2 were highly correlated with tumor size, depth of invasion, vessel invasion, lymph node metastasis and clinical stages. Univariate analysis of survival rate calculated by the Kaplan-Meier method revealed that gastric cancer patients with high-level EZH2 expression had poorer prognosis than those expressing no or low levels of EZH2 (P = 0.0271). These findings suggest that overexpression of EZH2 may contribute to the progression and oncogenesis of human gastric cancers, and thus immunohistochemical study of EZH2 expression may serve as a new biomarker for predicting the prognosis of gastric cancers.
已知基因转录抑制因子zeste同源物2(EZH2)蛋白的过表达与前列腺癌及其他几种癌症的生物学恶性程度相关。本研究旨在检测EZH2的表达,并分析其与人类胃癌临床病理特征的关系。检测了13种胃癌细胞系和83例手术切除的人类胃癌组织中EZH2 mRNA和蛋白的表达水平。对83份组织样本及相应的非癌性胃黏膜进行免疫组织化学分析,结果显示,EZH2在癌组织中的表达高于非癌组织,且EZH2的表达水平与肿瘤大小、浸润深度、血管浸润、淋巴结转移及临床分期高度相关。采用Kaplan-Meier法计算生存率的单因素分析显示,EZH2高表达的胃癌患者预后比不表达或低表达EZH2的患者差(P = 0.0271)。这些发现表明,EZH2的过表达可能促进人类胃癌的进展和肿瘤发生,因此,EZH2表达的免疫组织化学研究可作为预测胃癌预后的新生物标志物。