Methylation of the candidate biomarker TCF21 is very frequent across a spectrum of early-stage nonsmall cell lung cancers.
Methylation of the candidate biomarker TCF21 is very frequent across a spectrum of early-stage nonsmall cell lung cancers.
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DOI：
10.1002/cncr.25472
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发表时间：
2011-02-01
期刊：
影响因子：
6.2
通讯作者：
Krahe, Ralf
中科院分区：
文献类型：
--
作者：
Richards, Kristy L.;Zhang, Baili;Sun, Menghong;Dong, Wenli;Churchill, Jennifer;Bachinski, Linda L.;Wilson, Charmaine D.;Baggerly, Keith A.;Yin, Guosheng;Hayes, D. Neil;Wistuba, Ignacio I.;Krahe, Ralf
转录因子 TCF21 参与间充质到上皮细胞的分化，并显示在肺癌和头颈癌中异常高甲基化。由于据报道肺癌中高甲基化频率很高，我们试图描述高甲基化非小细胞肺癌 (NSCLC) 的阶段和类型，并定义高甲基化频率和相关的“第二次打击”。我们确定了 105 例 NSCLC 中的 TCF21 启动子高甲基化，包括吸烟者和非吸烟者的各个阶段和组织学。此外，我们还检查了 TCF21 杂合性丢失和突变状态。我们还分析了来自不同组织来源的 22 种癌细胞系。我们通过检查包含 300 个 NSCLC 病例的组织微阵列上的 TCF21 免疫组织化学表达来验证和扩展我们的 NSCLC 结果。总体而言，81% 的 NSCLC 样本显示 TCF21 启动子高甲基化，84% 显示 TCF21 蛋白表达下降。多变量分析显示，TCF21 表达虽然在两种组织学中都低于正常值，但在腺癌中低于鳞状细胞癌，并且与性别、吸烟和 EGFR 突变状态或临床结果不独立相关。来自其他癌症类型的细胞系也表现出频繁的 TCF21 启动子高甲基化。 TCF21 的高甲基化和表达降低具有肿瘤特异性，并且在所有 NSCLC 中非常常见，甚至在早期疾病中也很常见，因此使 TCF21 成为早期 NSCLC 筛查的潜在候选甲基化生物标志物。 TCF21 在多种肿瘤细胞系中的高甲基化表明它也可能是其他肿瘤类型中有价值的甲基化生物标志物。
The transcription factor TCF21 is involved in mesenchymal-to-epithelial differentiation and was shown to be aberrantly hypermethylated in lung and head and neck cancers. Because of its reported high frequency of hypermethylation in lung cancer, we sought to characterize the stages and types of non-small cell lung cancer (NSCLC) that are hypermethylated and to define the frequency of hypermethylation and associated “second hits”. We determined TCF21 promoter hypermethylation in 105 NSCLC including various stages and histologies in smokers and nonsmokers. Additionally, we examined TCF21 loss-of-heterozygosity and mutational status. We also assayed 22 cancer cell lines from varied tissue origins. We validated and expanded our NSCLC results by examining TCF21 immunohistochemical expression on a tissue microarray containing 300 NSCLC cases. Overall, 81% of NSCLC samples showed TCF21 promoter hypermethylation and 84% showed decreased TCF21 protein expression. Multivariate analysis showed that TCF21 expression, although below normal in both histologies, was lower in adenocarcinoma than squamous cell carcinoma, and was not independently correlated with gender, smoking and EGFR mutation status, or clinical outcome. Cell lines from other cancer types also showed frequent TCF21 promoter hypermethylation. Hypermethylation and decreased expression of TCF21 were tumor-specific and very frequent in all NSCLC, even early-stage disease, thus making TCF21 a potential candidate methylation biomarker for early-stage NSCLC screening. TCF21 hypermethylation in a variety of tumor cell lines suggests it may also be a valuable methylation biomarker in other tumor types.
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影响因子：
2.7
作者：
Colella, S;Shen, L;Krahe, R
通讯作者：
Krahe, R
影响因子：
158.5
作者：
Thompson, IM;Pauler, DK;Coltman, CA
通讯作者：
Coltman, CA
DOI：
10.1073/pnas.0510171102
发表时间：
2006-01-24
影响因子：
11.1
作者：
Smith, LT;Lin, MT;Plass, C
通讯作者：
Plass, C
影响因子：
14.9
作者：
Griffiths-Jones S;Grocock RJ;van Dongen S;Bateman A;Enright AJ
通讯作者：
Enright AJ
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P