Dong Min, Fan Xin-Juan, Chen Zhan-Hong, Wang Tian-Tian, Li Xing, Chen Jie, Lin Qu, Wen Jing-Yun, Ma Xiao-Kun, Wei Li, Ruan Dan-Yun, Lin Ze-Xiao, Liu Quentin, Wu Xiang-Yuan, Wan Xiang-Bo
Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, P.R. China.
Department of Pathology, Gastrointestinal Institute, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, P.R. China.
Oncol Rep. 2014 Sep;32(3):1101-7. doi: 10.3892/or.2014.3322. Epub 2014 Jul 10.
Overexpression of enhancer of zeste homologue 2 (EZH2), a key component of polycomb proteins, has been linked to aggressive tumor behavior in a variety of cancers. In vitro, hypoxia-inducible factor 1α (HIF-1α) transcriptionally activates EZH2 and promotes the progression of breast tumor initiating cells. Here, we characterized the clinicopathological effect of EZH2 and HIF-1α in 410 breast cancer patients. We examined EZH2 and HIF-1α expression using immunohistochemistry and western blotting. We found that EZH2 and HIF-1α were highly expressed in 99 (24.1%) and 272 (70.6%) patients, respectively. EZH2 overexpression was associated with lymphatic invasion (P=0.025), HER2 expression (P=0.005) and hypoxia (P<0.001). Overexpression of EZH2 predicted a poor 5-year overall survival (OS, 74.8 vs. 93.4%, P=0.001), disease-free survival (DFS, 72.2 vs. 88.6%, P=0.031), local failure-free survival (LFFS, 95.7 vs. 97.9%, P=0.045) and distant metastasis-free survival (DMFS, 75.4 vs. 90.5%, P=0.039). Multivariate analysis confirmed that EZH2 is an independent prognostic factor for OS, DFS and LFFS. Moreover, a positive correlation was identified between EZH2 and HIF-1α (r=0.299, P<0.001). Importantly, tumors coexpressing HIF-1α and EZH2 had a poorer OS (P=0.007). In conclusion, our study demonstrated that EZH2 is an independent negative prognostic biomarker for breast cancer. Tumors overexpressing HIF-1α and EZH2 are more prone to disease progression.
多梳蛋白的关键成分zeste同源物2（EZH2）的过表达与多种癌症中的侵袭性肿瘤行为有关。在体外，缺氧诱导因子1α（HIF-1α）转录激活EZH2并促进乳腺肿瘤起始细胞的进展。在此，我们对410例乳腺癌患者中EZH2和HIF-1α的临床病理效应进行了表征。我们使用免疫组织化学和蛋白质印迹法检测EZH2和HIF-1α的表达。我们发现EZH2和HIF-1α分别在99例（24.1%）和272例（70.6%）患者中高表达。EZH2过表达与淋巴浸润（P=0.025）、HER2表达（P=0.005）和缺氧（P<0.001）相关。EZH2过表达预示着5年总生存率（OS，74.8%对93.4%，P=0.001）、无病生存率（DFS，72.2%对88.6%，P=0.031）、局部无复发生存率（LFFS，95.7%对97.9%，P=0.045）和远处无转移生存率（DMFS，75.4%对90.5%，P=0.039）较差。多变量分析证实EZH2是OS、DFS和LFFS的独立预后因素。此外，EZH2和HIF-1α之间存在正相关（r=0.299，P<0.001）。重要的是，共表达HIF-1α和EZH2的肿瘤OS较差（P=0.007）。总之，我们的研究表明EZH2是乳腺癌的独立阴性预后生物标志物。过表达HIF-1α和EZH2的肿瘤更易发生疾病进展。
