Abnormal methylation of seven genes and their associations with clinical characteristics in early stage non-small cell lung cancer.
Abnormal methylation of seven genes and their associations with clinical characteristics in early stage non-small cell lung cancer.
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早期非小细胞肺癌7个基因异常甲基化及其与临床特征的关系
DOI：
10.3892/ol.2013.1161
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发表时间：
2013-04
期刊：
影响因子：
2.9
通讯作者：
Lin Q
中科院分区：
文献类型：
--
作者：
Zhao Y;Zhou H;Ma K;Sun J;Feng X;Geng J;Gu J;Wang W;Zhang H;He Y;Guo S;Zhou X;Yu J;Lin Q
为了发现早期非小细胞肺癌（NSCLC）中新的异常甲基化基因，我们分析了13个基因的甲基化状态（ALX 1、BCL 2、FOXL2、HPP 1、MYF 6、OC 2、PDGFRA、PHOX2A、PITX 2、RARB、SIX6、SMPD 3和SOX 1），使用甲基化特异性PCR（MSP）。MYF 6、SIX 6、SOX 1、RARB、BCL 2、PHOX 2A和FOLX 2 7个基因在I期NSCLC中的甲基化频率（29.70-64.36%）显著高于非癌性肺疾病对照组（P<0.05）。SIX 6和SOX 1、SIX 6、RARB和SOX 1的共甲基化与腺鳞癌（adenosquamous carcinoma，ADC）相关，BCL 2、RARB和SIX 6的共甲基化与吸烟相关。MYF 6、SIX 6、BCL 2和RARB 4个基因联合检测诊断I期NSCLC的敏感性为93.07%，特异性为83.33%。此外，我们还采用免疫组化法检测了I期NSCLC组织中8种病理标志物（VEGF、HER-2、P53、P21、EGFR、CHGA、SYN和EMA）的表达，发现p53和CHGA的高表达分别与BCL 2（P=0.025）和PHOX 2A（P=0.023）的甲基化相关。在本研究中，与非癌性肺部疾病相比，在I期NSCLC中表现出高甲基化的7个基因中，首次发现5个基因（MYF 6、SIX 6、PHOX 2A、FOLX 2和SOX 1）在NSCLC中异常甲基化。对这些基因的进一步研究有助于阐明NSCLC的致癌机制。
To identify novel abnormally methylated genes in early stage non-small cell lung cancer (NSCLC), we analyzed the methylation status of 13 genes (ALX1, BCL2, FOXL2, HPP1, MYF6, OC2, PDGFRA, PHOX2A, PITX2, RARB, SIX6, SMPD3 and SOX1) in cancer tissues from 101 cases of stage I NSCLC patients and lung tissues from 30 cases of non-cancerous lung disease controls, using methylation-specific PCR (MSP). The methylation frequencies (29.70–64.36%) of 7 genes (MYF6, SIX6, SOX1, RARB, BCL2, PHOX2A and FOLX2) in stage I NSCLC were significantly higher compared with those in non-cancerous lung disease controls (P<0.05). The co-methylation of SIX6 and SOX1, or the co-methyaltion of SIX6, RARB and SOX1 was associated with adenosquamous carcinoma (ADC), and the co-methylation of BCL2, RARB and SIX6 was associated with smoking. A panel of 4 genes (MYF6, SIX6, BCL2 and RARB) may offer a sensitivity of 93.07% and a specificity of 83.33% in the diagnosis of stage I NSCLC. Furthermore, we also detected the expression of 8 pathological markers (VEGF, HER-2, P53, P21, EGFR, CHGA, SYN and EMA) in cancer tissues of stage I NSCLC by immunohistochemistry, and found that high expression levels of p53 and CHGA were associated with the methylation of BCL2 (P=0.025) and PHOX2A (P=0.023), respectively. In this study, among the 7 genes which demonstrated hypermethylation in stage I NSCLC compared with non-cancerous lung diseases, 5 genes (MYF6, SIX6, PHOX2A, FOLX2 and SOX1) were found for the first time to be abonormally methylated in NSCLC. Further study of these genes shed light on the carcinogenesis of NSCLC.
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影响因子：
11.2
作者：
Lin, Ruo-Kai;Wu, Chiu-Yi;Wang, Yi-Ching
通讯作者：
Wang, Yi-Ching
影响因子：
--
作者：
Rauch, Tibor A.;Wang, Zunde;Pfeifer, Gerd P.
通讯作者：
Pfeifer, Gerd P.
影响因子：
37.3
作者：
Mathews LA;Hurt EM;Zhang X;Farrar WL
通讯作者：
Farrar WL
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影响因子：
11.5
作者：
Yu, Jian;Zhu, Tongyu;Zhu, Jingde
通讯作者：
Zhu, Jingde
影响因子：
6.6
作者：
Ma, Zhiyong;Tsuchiya, Norihiko;Habuchi, Tomonori
通讯作者：
Habuchi, Tomonori