Sox17 promoter methylation in plasma DNA is associated with poor survival and can be used as a prognostic factor in breast cancer.
Sox17 promoter methylation in plasma DNA is associated with poor survival and can be used as a prognostic factor in breast cancer.
复制标题
血浆 DNA 中的 Sox17 启动子甲基化与生存率低相关，可作为乳腺癌的预后因素。
DOI：
10.1097/md.0000000000000637
复制
发表时间：
2015-03
期刊：
影响因子：
1.6
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Fu D;Ren C;Tan H;Wei J;Zhu Y;He C;Shao W;Zhang J
已知导致肿瘤抑制基因失活的异常DNA甲基化在乳腺癌的发展和进展中起重要作用。肿瘤相关基因的甲基化状态被认为是肿瘤早期诊断和预后的一个有前途的生物标志物。本研究通过检测乳腺癌组织及相应血浆DNA中Sox 17基因的甲基化状态，探讨其与临床病理参数及预后的关系。采用甲基化特异性聚合酶链反应（MSP）对155对乳腺癌组织和血浆样本以及60对正常乳腺组织和血浆样本中Sox 17基因启动子的甲基化状态进行了评估。采用χ2检验分析Sox 17甲基化状态与临床病理参数的关系。使用Kaplan-Meier分析计算总体和无病生存（DFS）曲线，并通过对数秩检验分析曲线之间的差异。Sox 17基因甲基化在乳腺癌组织中的发生率为72.9%（113/155），在血浆DNA中的发生率为58.1%（90/155）。Sox 17基因甲基化在正常乳腺组织及其配对的血浆DNA中未发现。Sox 17甲基化在相应肿瘤组织与配对血浆DNA之间存在显著相关性（r = 0.688，P <0.001）。 癌组织和血浆DNA中Sox 17异常甲基化与肿瘤淋巴结转移分期（P = 0.035和P = 0.001）和淋巴结转移（P <0.001和P = 0.001）显著相关。 Kaplan-Meier生存曲线显示，肿瘤组织和血浆DNA中Sox 17启动子甲基化与DFS和总生存期（OS）差相关（P <0.005）。 多变量分析显示，血浆DNA中Sox 17甲基化是乳腺癌DFS（P = 0.020;风险比[HR]= 2.142; 95%置信区间[CI]：1.128-4.067）和OS（P = 0.001; HR = 4.737; 95% CI：2.088-10.747）的独立预后因素。 Sox 17基因启动子甲基化可能在乳腺癌的进展中起重要作用，并可作为一种预后生物标志物，用于识别乳腺癌术后发生转移或复发的风险。
Supplemental Digital Content is available in the text Aberrant DNA methylation that leads to the inactivation of tumor suppressor genes is known to play an important role in the development and progression of breast cancer. Methylation status of cancer-related genes is considered to be a promising biomarker for the early diagnosis and prognosis of tumors. This study investigated the methylation status of the Sox17 gene in breast cancer tissue and its corresponding plasma DNA to evaluate the association of methylation levels with clinicopathological parameters and prognosis. The methylation status of the Sox17 gene promoter was evaluated with methylation-specific polymerase chain reaction (MSP) in 155 paired breast cancer tissue and plasma samples and in 60 paired normal breast tissue and plasma samples. Association of Sox17 methylation status with clinicopathological parameters was analyzed by χ2 tests. Overall and disease-free survival (DFS) curves were calculated using Kaplan–Meier analysis, and the differences between curves were analyzed by log-rank tests. The frequency of Sox17 gene methylation was 72.9% (113/155) in breast cancer tissues and 58.1% (90/155) in plasma DNA. Sox17 gene methylation was not found in normal breast tissues or in their paired plasma DNA. There was a significant correlation of Sox17 methylation between corresponding tumor tissues and paired plasma DNA (r = 0.688, P < 0.001). Aberrant Sox17 methylation in cancer tissues and in plasma DNA was significantly associated with the tumor node metastasis stage (P = 0.035 and P = 0.001, respectively) and with lymph node metastasis (P < 0.001 and P = 0.001, respectively). Kaplan–Meier survival curves showed that aberrant Sox17 promoter methylation in cancer tissues and plasma DNA was associated with poor DFS (P < 0.005) and overall survival (OS) (P < 0.005). Multivariate analysis showed that Sox17 methylation in plasma DNA was an independent prognostic factor in breast cancer for both DFS (P = 0.020; hazard ratio [HR] = 2.142; 95% confidence interval [CI]: 1.128–4.067) and for OS (P = 0.001; HR = 4.737; 95% CI: 2.088–10.747). Sox17 gene promoter methylation may play an important role in breast cancer progression and could be used as a prognostic biomarker to identify patients at risk of developing metastasis or recurrence after mastectomy.