Hypermethylation of the TSLC1/IGSF4 promoter is associated with tobacco smoking and a poor prognosis in primary nonsmall cell lung carcinoma
Hypermethylation of the TSLC1/IGSF4 promoter is associated with tobacco smoking and a poor prognosis in primary nonsmall cell lung carcinoma
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DOI：
10.1002/cncr.21800
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发表时间：
2006-04-15
期刊：
影响因子：
6.2
通讯作者：
Murakami, Y
中科院分区：
文献类型：
--
作者：
Kikuchi, S;Yamada, D;Murakami, Y
背景。染色体区域 11q23 上的肿瘤抑制基因 TSLC1/IGSF4 在各种癌症（包括非小细胞肺癌 (NSCLC)）中经常因启动子甲基化而失活。多项研究表明，CpG 基因岛（包括肿瘤抑制基因）的高甲基化与接触烟草烟雾有关。本研究的目的是通过大量原发性NSCLC研究TSLC1/CSF4甲基化与吸烟以及肿瘤临床特征的可能关联。方法。在 103 个原发性 NSCLC 中分析了 TSLC1/IGSF-4 的启动子甲基化。通过逆转录聚合酶链式反应（RT-PCR）和免疫组织化学检测TSLC1/IGSF4的表达，并通过亚硫酸氢盐单链构象多态性（SSCP）结合亚硫酸氢盐测序测定其甲基化状态。 结果。 103 个原发性 NSCLC 中有 45 个 (44%) 的 TSLC1/IGSF4 启动子被甲基化。在 NSCLC 的所有组织学亚型中均观察到甲基化，包括腺癌（68 个中的 29 个，43%）、鳞状细胞癌（26 个中的 14 个，54%）、腺鳞癌（2 个 I，50%）和大细胞癌（7 个 I，14%）。男性患者甲基化不良肿瘤的发生率显着高于女性患者 (P = .027)。 TSLC1/IGSF4 甲基化优先在重度吸烟者（吸烟指数 >= 800）中观察到（P = .0054）。此外，在吸烟者中，甲基化与吸烟包年数 (P = .034) 和每支香烟的数量 (P = .021) 显着相关。 TSLC1/IGSF4 甲基化还与较短的无病生存期显着相关 (P = .049)，为腺癌患者提供了一个独立的预后因素 (P = .038)。结论。 TSLC1/IGSF4 甲基化与吸烟有关，可能是预后不良的指标。
BACKGROUND. The tumor Suppressor gene TSLC1/IGSF4 on chromosomal region 11q23 is frequently inactivated by promoter methylation in various cancers, including nonsmall cell lung carcinoma (NSCLC). Several Studies have demonstrated that the hypermethylation of the CpG islands of genes, including tumor suppressors, is associated with exposure to tobacco smoke. The purpose Of this Study was to investigate the possible association of TSLC1/CSF4 methylation with tobacco smoking as well as with the clinical characteristics of tumors using a large number of primary NSCLC.METHODS. The promoter methylation of TSLC1/IGSF-4 was analyzed in 103 primary NSCLC. TSLC1/IGSF4 expression was examined by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, whereas its methylation status was determined by bisulfite single-strand conformation polymorphism (SSCP) Coupled with bisulfite sequencing.RESULTS. The TSLC1/IGSF4 promoter was methylated in 45 (44%) of 103 primary NSCLC. Methylation was observed in all histologic subtypes of NSCLC, including adenocarcinoma (29 of 68, 43%), squamous Cell carcinoma (14 of 26, 54%), adenosquamous carcinoma (I of 2, 50%), and large cell carcinoma (I of 7, 14%). The incidence of methylation ill tumors was significantly higher in male patients than in female patients (P = .027). The TSLC1/IGSF4 methylation was preferentially observed in heavy smokers (smoking index >= 800) (P = .0054). Furthermore, in smokers the methylation was significantly associated with pack-years smoked (P = .034) and cigarettes per clay (P = .021). The TSLC1/IGSF4 methylation was also significantly associated with a shorter disease-free survival (P = .049), providing an independentt prognostic factor (P = .038) in adenocarcinoma patients.CONCLUSIONS. TSLC1/IGSF4 methylation is associated with tobacco smoking and could be all indicator of poor prognosis.