H3K27me3 Protein Is a Promising Predictive Biomarker of Patients' Survival and Chemoradioresistance in Human Nasopharyngeal Carcinoma
H3K27me3 Protein Is a Promising Predictive Biomarker of Patients' Survival and Chemoradioresistance in Human Nasopharyngeal Carcinoma
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DOI：
10.2119/molmed.2011.00054
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发表时间：
2011-11-01
影响因子：
5.7
通讯作者：
Xie, Dan
中科院分区：
文献类型：
--
作者：
Cai, Mu-Yan;Tong, Zhu-Ting;Xie, Dan
组蛋白H3上赖氨酸27的三甲基化（H3 K27 me 3）是一种表观遗传变化，其在肿瘤的发生和/或进展中起关键作用。然而，H3 K27 me 3的分子状态及其在鼻咽癌（NPC）中的临床病理/预后意义尚未阐明。本研究采用Western blotting和免疫组织化学（MHC）方法检测H3 K27 me 3蛋白在NPC组织和非肿瘤鼻咽上皮组织中的表达。使用受试者工作特征（ROC）曲线分析来确定H3 K27 me 3高表达的临界点。H3 K27 me 3在鼻咽癌组织中的阳性表达率为60.8%（127/209），在正常鼻咽上皮组织中的阳性表达率为16.0%（8/50）（P < 0.001）。进一步相关分析显示H3 K27 me 3高表达与肿瘤T分期晚、有无转移、临床分期高、放化疗耐药有关（P < 0.05）。单因素和多因素分析显示H3 K27 me 3高表达与鼻咽癌患者生存期缩短密切相关（P < 0.05）。因此，一个新的临床病理预后模型与三个不良预后因素（H3 K27 me 3表达，远处转移和治疗方案）的构建。该模型可以显著地将总生存期和无进展生存期的风险分层（低、中、高）（P < 0.0001）。这些发现提供了证据表明，H3 K27 me 3表达，如通过IHC检查，有可能用作免疫标记物来预测NPC放化疗反应和患者预后。联合临床病理预后模型可能成为一个有用的工具，以确定不同的临床结果的鼻咽癌患者。(C)2011 Feinstein医学研究所，www.feinsteininstitute.org在线地址：http://www.molmed.org doi：10.2119/molmed.2011.00054
Trimethylation of lysine 27 on histone H3 (H3K27me3) is an epigenetic change which plays a critical role in tumor development and/or progression. However, the molecular status of H3K27me3 and its clinicopathologic/prognostic significance in nasopharyngeal carcinoma (NPC) have not been elucidated. In this study, the methods of Western blotting and immunohistochemistry (IHC) were utilized to examine the expression of H3K27me3 protein in NPC tissues and nonneoplastic nasopharyngeal epithelial tissues. Receiver operating characteristic (ROC) curve analysis was used to determine the cutpoint for H3K27me3 high expression. High expression of H3K27me3 could be observed in 127/209 (60.8%) of NPCs and in 8/50 (16.0%) normal nasopharyngeal epithelial tissues (P < 0.001). Further correlation analysis demonstrated that high expression of H3K27me3 was positively associated with tumor later T classification, tumor metastasis, advanced clinical stage and chemoradioresistance (P < 0.05). Moreover, high expression of H3K27me3 was closely associated with NPC patient shortened survival time as evidenced by univariate and multivariate analysis (P < 0.05). Consequently, a new clinicopathologic prognostic model with three poor prognostic factors (H3K27me3 expression, distant metastasis and treatment regimen) was constructed. The model could stratify risk significantly (low, intermediate and high) for overall survival and progression-free survival (P < 0.0001). These findings provide evidence that H3K27me3 expression, as examined by IHC, has the potential to be used as an immunomarker to predict NPC chemoradiotherapy response and patient prognosis. The combined clinicopathologic prognostic model may become a useful tool for identifying NPC patients with different clinical outcomes. (C) 2011 The Feinstein Institute for Medical Research, www.feinsteininstitute.org Online address: http://www.molmed.org doi: 10.2119/molmed.2011.00054