DNA methylation markers and early recurrence in stage I lung cancer
DNA methylation markers and early recurrence in stage I lung cancer
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DOI：
10.1056/nejmoa0706550
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发表时间：
2008-03-13
影响因子：
158.5
通讯作者：
Herman, James G.
中科院分区：
文献类型：
--
作者：
Brock, Malcolm V.;Hooker, Craig M.;Herman, James G.
背景：尽管对非小细胞肺癌（NSCLC）进行了最佳和早期的手术治疗，但许多患者死于复发性NSCLC。我们研究了基因甲基化与肿瘤复发之间的关系。方法：51例行根治性切除但术后40个月内复发的I期非小细胞肺癌患者（病例患者）与116例行根治性切除但术后40个月内未复发的I期非小细胞肺癌患者（对照组）根据年龄、NSCLC分期、性别和手术日期进行匹配。我们研究了肿瘤和淋巴结中七个基因的甲基化是否与肿瘤复发有关。结果：在一个多变量模型中，肿瘤和组织学上肿瘤阴性淋巴结中细胞周期蛋白依赖性激酶抑制剂2A基因p16、h -钙粘蛋白基因CDH13、Ras关联结构域家族1基因RASSF1A和大肠腺瘤性息肉病基因APC的启动子甲基化与肿瘤复发相关，与NSCLC分期、年龄、性别、种族、吸烟史和肿瘤组织学特征无关。肿瘤和纵隔淋巴结中p16和CDH13启动子区域的甲基化与原始队列中复发癌症的比值比为15.50相关，当原始队列与20例I期NSCLC患者的独立验证队列合并时，比值比为25.25。结论：在手术治疗的I期NSCLC患者中，这四个基因的启动子区甲基化与早期复发有关。
Background: Despite optimal and early surgical treatment of non-small-cell lung cancer (NSCLC), many patients die of recurrent NSCLC. We investigated the association between gene methylation and recurrence of the tumor.Methods: Fifty-one patients with stage I NSCLC who underwent curative resection but who had a recurrence within 40 months after resection (case patients) were matched on the basis of age, NSCLC stage, sex, and date of surgery to 116 patients with stage I NSCLC who underwent curative resection but who did not have a recurrence within 40 months after resection (controls). We investigated whether the methylation of seven genes in tumor and lymph nodes was associated with tumor recurrence.Results: In a multivariate model, promoter methylation of the cyclin-dependent kinase inhibitor 2A gene p16, the H-cadherin gene CDH13, the Ras association domain family 1 gene RASSF1A, and the adenomatous polyposis coli gene APC in tumors and in histologically tumor-negative lymph nodes was associated with tumor recurrence, independently of NSCLC stage, age, sex, race, smoking history, and histologic characteristics of the tumor. Methylation of the promoter regions of p16 and CDH13 in both tumor and mediastinal lymph nodes was associated with an odds ratio of recurrent cancer of 15.50 in the original cohort and an odds ratio of 25.25 when the original cohort was combined with an independent validation cohort of 20 patients with stage I NSCLC.Conclusions: Methylation of the promoter region of the four genes in patients with stage I NSCLC treated with curative intent by means of surgery is associated with early recurrence.