CST6 promoter methylation in circulating cell-free DNA of breast cancer patients
CST6 promoter methylation in circulating cell-free DNA of breast cancer patients
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DOI：
10.1016/j.clinbiochem.2012.09.015
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发表时间：
2013-02-01
影响因子：
2.8
通讯作者：
Lianidou, Evi
中科院分区：
文献类型：
--
作者：
Chimonidou, Maria;Tzitzira, Alexandra;Lianidou, Evi
目的：我们最近发现CST6启动子甲基化的检测可以为可手术乳腺癌患者提供重要的预后信息，循环肿瘤细胞(CTC)中也存在CST6启动子甲基化。在这项研究中，我们评估了乳腺癌患者血浆中循环的游离DNA(CfDNA)中CST6启动子甲基化的存在。设计和方法：我们的研究材料包括：a)27例I-Ill期可手术乳腺癌患者，46例已证实转移的患者和37名健康献血者的先导试验组，以及b)123例连续I-Ill期可手术乳腺癌患者的独立队列。用甲基化特异性聚合酶链式反应(MSP)检测CST6启动子的甲基化和非甲基化。结果：在先导试验组中，27例可手术乳腺癌患者中8例(29.6%)CST6启动子甲基化，6/46例有转移患者(13.0%)CST6启动子甲基化，37例健康人(0%)CST6启动子甲基化。在独立队列中，49/123例(39.8%)可手术乳腺癌患者为阳性。随访期内复发25例(20.3%)，死亡9例(73%)。结论：CST6启动子在乳腺癌患者的cfDNA中存在高度甲基化，而在健康人中则不存在。CfDNA中CST6启动子的甲基化，应该作为一种新的乳腺癌血浆肿瘤生物标志物在大量乳腺癌患者中进行前瞻性验证。(C)2012年加拿大临床化学家学会。爱思唯尔公司出版，版权所有。
Objectives: We have recently shown that detection of CST6 promoter methylation in primary breast tumors can provide important prognostic information in patients with operable breast cancer and that CST6 promoter is also methylated in Circulating Tumor Cells (CTC). In this study we evaluated the presence of CST6 promoter methylation in cell-free DNA (cfDNA) circulating in plasma of breast cancer patients.Design and methods: Our study material consisted of: a) a pilot testing group of 27 patients with stage I-Ill operable breast cancer, 46 patients with verified metastasis and 37 healthy donors and b) an independent cohort of 123 consecutive stage I-Ill operable breast cancer patients. Methylated and unmethylated CST6 promoter sequences were detected by using methylation-specific PCR (MSP). CST6 immunohistochemical detection was performed in 20 corresponding primary tumor tissues.Results: In the pilot testing group, CST6 promoter was methylated in 8/27 (29.6%) operable breast cancer patients, in 6/46 (13.0%) patients with verified metastasis but none of 37 healthy individuals (0%). In the independent cohort 49/123 (39.8%) operable breast cancer patients were found positive. During the follow up period, 25/123 (20.3%) patients relapsed and 9/123 (73%) died. CST6 was methylated in cfDNA of 13/25 (52%) patients that relapsed and in 3/9 (33.3%) patients that died.Conclusions: CST6 promoter is highly methylated in cfDNA of breast cancer patients, but not in healthy individuals. CST6 promoter methylation in cfDNA, should be prospectively validated as a novel plasma tumor biomarker for breast cancer in a large cohort of breast cancer patients. (C) 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.