Department of Epidemiology, School of Public Health, University of Washington, Box 359933, Seattle, WA 98195, USA.
Lung Cancer. 2010 Aug;69(2):172-9. doi: 10.1016/j.lungcan.2009.11.002. Epub 2009 Nov 28.
We previously identified a number of genes which were methylated significantly more frequently in the tumor compared to the non-cancerous lung tissues from non-small cell lung cancer (NSCLC) patients. Detection of methylation profiles of genes in NSCLC could provide insight into differential pathways to malignancy and lead to strategies for better treatment of individuals with NSCLC.
We determined the DNA methylation status of 27 genes using quantitative MethyLight assays in lung tumor samples from 117 clinically well-characterized NSCLC patients.
Hypermethylation was detected in one of more of the genes in 106 (91%) of 117 cases and was detected at high levels (percentage methylation reference (PMR)> or =4%) in 79% of NSCLC cases. Methylation of APC, CCND2, KCNH5 and, RUNX was significantly more frequent in adenocarcinomas compared to squamous cell carcinomas (SCC), while methylation of CDKN2A was more common in SCC. Hypermethylation of KCNH5, KCNH8, and RARB was more frequent in females compared to males. Hypermethylation of APC and CCND2 was inversely associated with proliferation score assessed by Ki-67 level.
Our findings of differential gene hypermethylation frequencies in tumor tissues from patients with adenocarcinoma or squamous cell cancers and in females compared to males suggests that further investigation is warranted in order to more fully understand the potential disparate pathways and/or risk factors for NSCLC associated with histologic type and gender.
我们之前发现了一些在非小细胞肺癌（NSCLC）患者的肿瘤组织中比非癌性肺组织中甲基化频率显著更高的基因。检测 NSCLC 中基因的甲基化谱可以深入了解恶性转化的差异途径，并为更好地治疗 NSCLC 患者提供策略。
我们使用定量 MethyLight 测定法在 117 例临床特征明确的 NSCLC 患者的肺肿瘤样本中检测了 27 个基因的 DNA 甲基化状态。
在 117 例病例中，106 例（91%）检测到一个或多个基因的过度甲基化，79%的 NSCLC 病例中检测到高水平甲基化（甲基化百分比参考值（PMR）≥4%）。APC、CCND2、KCNH5 和 RUNX 的甲基化在腺癌中比鳞状细胞癌（SCC）更为频繁，而 CDKN2A 的甲基化在 SCC 中更为常见。KCNH5、KCNH8 和 RARB 的过度甲基化在女性中比男性更为频繁。APC 和 CCND2 的过度甲基化与 Ki-67 水平评估的增殖评分呈负相关。
我们发现腺癌或鳞状细胞癌患者肿瘤组织和女性与男性相比基因过度甲基化频率的差异表明，需要进一步研究以更全面地了解与组织学类型和性别相关的 NSCLC 的潜在不同途径和/或风险因素。
