Promoter hypermethylation of the CFTR gene as a novel diagnostic and prognostic marker of breast cancer
Promoter hypermethylation of the CFTR gene as a novel diagnostic and prognostic marker of breast cancer
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CFTR 基因启动子高甲基化作为乳腺癌的新型诊断和预后标志物
DOI：
10.1002/cbin.11260
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发表时间：
2020-02-01
影响因子：
3.9
通讯作者：
Zou, Chang
中科院分区：
文献类型：
--
作者：
Liu, Kaisheng;Dong, Fajin;Zou, Chang
乳腺癌是最常见的癌症，也是妇女癌症相关死亡的主要原因。迫切需要具有明确诊断和预后功效的新生物标志物。在这里，我们发现囊性纤维化跨膜传导调节因子（CFTR）的启动子在乳腺癌中高甲基化。乳腺癌组织中CFTR mRNA水平下调。值得注意的是，所有19例CFTR高甲基化的乳腺癌患者均被诊断为浸润性癌。此外，CFTR在地西他滨（10 μ M）处理的乳腺癌细胞中上调。CFTR的过表达抑制细胞生长，而CFTR的敲低促进细胞侵袭。在组织阵列分析中，CFTR蛋白水平在乳腺癌中显著降低，低CFTR蛋白水平与较差的存活率相关，P值为0.034。因此，CFTR基因启动子区甲基化可能是乳腺癌的一个新的诊断标志物。
Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer-related deaths among women. New biomarkers with definite diagnostic and prognostic efficacy are urgently needed. Here, we showed that the promoter of the cystic fibrosis transmembrane conductance regulator (CFTR) was hypermethylated in breast cancer. The messenger RNA level of CFTR was downregulated in breast cancer. Notably, all 19 breast cancer patients with hypermethylated CFTR were diagnosed with invasive carcinoma. Moreover, CFTR was upregulated in decitabine (10 mu M) treated breast cancer cells. Overexpression of CFTR inhibited cell growth whereas knockdown of CFTR promoted cell invasion. In the tissue array analysis, the CFTR protein level decreased significantly in breast cancer and low CFTR protein level correlated with poor survival with a P-value of 0.034. Thus, promoter hypermethylation of the CFTR gene might be a novel diagnostic marker of breast cancer.