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RUNX3 高甲基化对涎腺腺样囊性癌患者的临床预后不利。

Unfavorable clinical implications for hypermethylation of RUNX3 in patients with salivary gland adenoid cystic carcinoma.

机构信息

Department of Surgical Oncology, Zhejiang Province Cancer Hospital, Hangzhou 310022, PR China.

出版信息

Oncol Rep. 2011 Aug;26(2):349-57. doi: 10.3892/or.2011.1282. Epub 2011 Apr 28.

DOI:10.3892/or.2011.1282
PMID:21567090
Abstract

To elucidate the potential etiological role of RUNX3 in the development of salivary gland adenoid cystic carcinoma (ACC), we analyzed the methylation status of RUNX3 in a series of 114 ACC tissues and 3 ACC cell lines. Results showed that the methylated rate of RUNX3 was 50.9 and 3.5% in the 114 ACC samples and the corresponding normal salivary glands, respectively, achieving a significant difference (P<0.001). There was a significant correlation between RUNX3 methylation and various clinicopathological parameters of ACCs, such as perineural invasion, lymph node involvement, T-stage and distant metastasis (P<0.001). RUNX3 methylation was a significant predictor of the 5-year disease-free survival in ACC patients after surgery. Partial methylation was found in all 3 ACC cell lines, and the reactivation and more potent expression of RUNX3 was induced by 5-triazole-2-deoxycytidine. Our findings indicate that RUNX3 methylation may occur as a common event in the development of ACC and that methylation may be a major mechanism for inactivation of RUNX3 in ACC.

摘要

为了阐明 RUNX3 在唾液腺腺样囊性癌(ACC)发生发展中的潜在病因学作用,我们分析了 114 例 ACC 组织和 3 种 ACC 细胞系中 RUNX3 的甲基化状态。结果显示,在 114 例 ACC 样本和相应的正常唾液腺中,RUNX3 的甲基化率分别为 50.9%和 3.5%,差异具有统计学意义(P<0.001)。RUNX3 甲基化与 ACC 的各种临床病理参数,如神经周围侵犯、淋巴结转移、T 分期和远处转移均存在显著相关性(P<0.001)。RUNX3 甲基化是 ACC 患者术后 5 年无病生存率的显著预测因子。在所有 3 种 ACC 细胞系中均发现了部分甲基化,5-三唑-2-脱氧胞苷可诱导 RUNX3 的重新激活和更强烈的表达。我们的研究结果表明,RUNX3 甲基化可能是 ACC 发展中的一个常见事件,而甲基化可能是 ACC 中 RUNX3 失活的主要机制。

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