Brock Malcolm V, Hooker Craig M, Ota-Machida Emi, Han Yu, Guo Mingzhou, Ames Stephen, Glöckner Sabine, Piantadosi Steven, Gabrielson Edward, Pridham Genevieve, Pelosky Kristen, Belinsky Steven A, Yang Stephen C, Baylin Stephen B, Herman James G
Johns Hopkins Hospital, Baltimore, USA.
N Engl J Med. 2008 Mar 13;358(11):1118-28. doi: 10.1056/NEJMoa0706550.
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.
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.
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.
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.
尽管对非小细胞肺癌（NSCLC）进行了最佳的早期手术治疗，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联。
51例I期NSCLC患者接受了根治性切除，但在切除后40个月内复发（病例组），根据年龄、NSCLC分期、性别和手术日期，与116例I期NSCLC患者进行匹配，这些患者接受了根治性切除，但在切除后40个月内未复发（对照组）。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相关。
在多变量模型中，肿瘤及组织学上肿瘤阴性淋巴结中的细胞周期蛋白依赖性激酶抑制剂2A基因p16、H-钙黏蛋白基因CDH13、Ras关联结构域家族1基因RASSF1A和腺瘤性息肉病基因APC的启动子甲基化与肿瘤复发相关，独立于NSCLC分期、年龄、性别、种族、吸烟史和肿瘤的组织学特征。肿瘤和纵隔淋巴结中p16和CDH13启动子区域的甲基化与原队列中复发性癌症的比值比为15.50相关，当原队列与20例I期NSCLC患者的独立验证队列合并时，比值比为25.25。
通过手术进行根治性治疗的I期NSCLC患者中，四个基因启动子区域的甲基化与早期复发相关。
