头颈部鳞状细胞癌中TIMP3和CCNA1的高甲基化与第二原发性肿瘤的发病率增加有关。
TIMP3 and CCNA1 hypermethylation in HNSCC is associated with an increased incidence of second primary tumors.
作者信息
Rettori Marianna Marconato, de Carvalho Ana Carolina, Longo Ana Luiza Bomfim, de Oliveira Cleyton Zanardo, Kowalski Luiz Paulo, Carvalho André Lopes, Vettore André Luiz
机构信息
Cancer Molecular Biology Laboratory, Department of Biological Sciences, Federal University of São Paulo, 04039-020, São Paulo, Brazil.
出版信息
J Transl Med. 2013 Dec 20;11:316. doi: 10.1186/1479-5876-11-316.
BACKGROUND
Hypermethylation in the promoter regions is associated with the suppression of gene expression and has been considered a potential molecular marker for several tumor types, including head and neck squamous cell carcinomas (HNSCC).
METHODS
To evaluate the gene hypermethylation profile as a prognostic marker, this retrospective study used a QMSP approach to determine the methylation status of 19 genes in 70 HNSCC patients.
RESULTS
The methylation profile analysis of primary HNSCC revealed that genes CCNA1, DAPK, MGMT, TIMP3 and SFRP1 were frequently hypermethylated, with high specificity and sensitivity. TIMP3 and CCNA1 hypermethylation was significantly associated with lower rates of second primary tumor-free survival (p = 0.007 and p = 0.001; log-rank test, respectively).
CONCLUSION
This study, for the first time, presents CCNA1 and TIMP3 hypermethylation as a helpful tool to identify HNSCC subjects at risk of developing second primary carcinomas.
背景
启动子区域的高甲基化与基因表达抑制相关，并且已被认为是包括头颈部鳞状细胞癌（HNSCC）在内的几种肿瘤类型的潜在分子标志物。
方法
为了评估基因高甲基化谱作为一种预后标志物，这项回顾性研究采用定量甲基化特异性PCR（QMSP）方法来确定70例HNSCC患者中19个基因的甲基化状态。
结果
原发性HNSCC的甲基化谱分析显示，CCNA1、DAPK、MGMT、TIMP3和SFRP1基因经常发生高甲基化，具有高特异性和敏感性。TIMP3和CCNA1高甲基化与无第二原发性肿瘤生存率较低显著相关（分别为p = 0.007和p = 0.001；对数秩检验）。
结论
本研究首次提出CCNA1和TIMP3高甲基化是识别有发生第二原发性癌风险的HNSCC患者的有用工具。
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