Differential expression of RUNX genes in human esophageal squamous cell carcinoma:: Downregulation of RUNX3 worsens patient prognosis
Differential expression of RUNX genes in human esophageal squamous cell carcinoma:: Downregulation of RUNX3 worsens patient prognosis
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DOI：
10.1159/000135350
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发表时间：
2007-01-01
期刊：
影响因子：
3.5
通讯作者：
Nagasue, Naofumi
中科院分区：
文献类型：
--
作者：
Tonomoto, Yasuhito;Tachibana, Mitsuo;Nagasue, Naofumi
背景资料：RUNX蛋白是在胚胎发生和发育过程中具有重要功能的转录因子家族，而RUNX表达的失调通常与肿瘤形成有关。到目前为止，还没有研究描述食管鳞状细胞癌中RUNXs的精确表达、预后影响和甲基化状态。方法：采用实时荧光定量RT-PCR方法检测61例食管鳞癌组织中RUNX 1、RUNX 2和RUNX 3的表达。采用原位杂交技术对mRNA进行定位，免疫组化法检测Smad 4的表达，甲基化特异性PCR法检测RUNX 3的甲基化状态。结果：RUNX 3对患者预后有显著影响，RUNX 3阴性组的生存率更差。在早期肿瘤（T1/T2）中，RUNX 3阴性肿瘤中淋巴管浸润的患病率和转移性淋巴结的数量显著较高。此外，RUNX 3仅在Smad 4阳性肿瘤中成为强预后因子。此外，RUNX 3启动子的甲基化状态与RUNX 3表达的缺失具有显著相关性。结论：RUNX 3基因表达下调可能在食管鳞癌的发生发展中起一定作用，RUNX 3基因启动子区甲基化可能是其沉默的重要途径之一。版权所有（c）2008 S. Karger AG，巴塞尔。
Background: The RUNX proteins are a family of transcriptional factors that have essential functions during embryogenesis and development, whereas deregulation in expression of RUNXs is often linked to tumor formation. To date, there has been no study describing the precise expression, prognostic impact and methylation status of RUNXs in esophageal squamous cell carcinoma. Methods: Resected specimens from 61 patients with esophageal SCC were used to identify the expression of RUNX1, RUNX2 and RUNX3 by real-time RT-PCR. Localization of mRNA was done by in situ hybridization, expression of Smad4 was evaluated by immunohistochemistry, and the methylation status of RUNX3 was analyzed by methylation-specific PCR. Results: RUNX3 had a significant impact on patient prognosis with worse survival in the RUNX3-negative group. In early tumors (T1/T2), the prevalence of lymph vessel invasion and the number of metastatic lymph nodes were significantly higher in RUNX3-negative tumors. Furthermore, RUNX3 became a strong prognostic factor only in Smad4-positive tumors. Also, the methylation status of the RUNX3 promoter had a significant correlation with the loss of RUNX3 expression. Conclusion: Downregulation of RUNX3 may play a role in disease progression of esophageal SCC, and hypermethylation of the promoter region might be one of the crucial pathways to silence RUNX3 gene. Copyright (c) 2008 S. Karger AG, Basel.