非小细胞肺癌患者手术后无病生存与切除修复交叉互补基因 1 表达和基因型的相关性。

Disease-free survival of patients after surgical resection of non-small cell lung carcinoma and correlation with excision repair cross-complementation group 1 expression and genotype.

机构信息

Department of Medicine, Chonnam National University Hwasun Hospital, Jeonnam, South Korea.

出版信息

Respirology. 2012 Jan;17(1):127-33. doi: 10.1111/j.1440-1843.2011.02060.x.

DOI:10.1111/j.1440-1843.2011.02060.x

PMID:21899657

Abstract

BACKGROUND AND OBJECTIVE

Expression of excision repair cross-complementation group 1 (ERCC1) is recognized as a favourable prognostic marker in patients who have undergone surgical resection of non-small cell lung cancer (NSCLC). However, in patients treated with adjuvant chemotherapy after surgical resection, ERCC1 correlated with poor prognosis. Class III beta tubulin (TUBB3) is also known to be a predictive marker of the efficacy of treatment with taxanes or vinorelbine.

METHODS

Tumour tissues (n = 363) from patients with surgically resected NSCLC were analysed retrospectively. Tissue sections were labelled with ERCC1- and TUBB3-specific antibodies. Using genomic DNA from 262 patients, single nucleotide polymorphisms of the ERCC1 gene (T19007C and C8092A) were genotyped by PCR-restriction fragment length polymorphism analysis.

RESULTS

Only 5.9% of patients with stage I disease (14/238) and 61.6% of patients with stages II-III disease (77/125) received adjuvant chemotherapy. Relapses were noted in 30.6% (111) of patients, and among these, 31 ultimately succumbed. The relapse rate (RR) was 24.8% for stage I disease, and 41.6% for stages II-III disease. The RR was significantly lower in ERCC1-positive (24.3%) as compared with ERCC1-negative patients (36.3%, P = 0.014) and was lower in patients with the AA/CA genotype at the ERCC1 C8092A locus (29.5%) compared with those with the CC genotype (42.1%, P = 0.034). The median disease-free survival (DFS) time was 62.3 months. DFS was significantly greater in ERCC1-positive patients (62.3 months) than in ERCC1-negative patients (48.0 months, P = 0.042). In a multivariate analysis, ERCC1 expression and the C8092A polymorphism were independent prognostic factors in patients with stage I disease who were naïve to chemotherapy.

CONCLUSIONS

ERCC1 expression and the AA/CA genotype at the C8092A locus were correlated with a good prognosis in patients who had undergone surgical resection of NSCLC.

摘要

背景与目的

切除修复交叉互补基因 1（ERCC1）的表达被认为是接受非小细胞肺癌（NSCLC）手术切除的患者的有利预后标志物。然而，在接受手术后辅助化疗的患者中，ERCC1 与预后不良相关。III 类β微管蛋白（TUBB3）也被认为是紫杉烷类或长春瑞滨治疗疗效的预测标志物。

方法

回顾性分析了 363 例接受手术切除的 NSCLC 患者的肿瘤组织。组织切片用 ERCC1 和 TUBB3 特异性抗体标记。使用 262 例患者的基因组 DNA，通过 PCR-限制性片段长度多态性分析对 ERCC1 基因（T19007C 和 C8092A）的单核苷酸多态性进行基因分型。

结果

仅有 5.9%（14/238）的 I 期疾病患者和 61.6%（77/125）的 II-III 期疾病患者接受了辅助化疗。30.6%（111 例）的患者出现复发，其中 31 例最终死亡。I 期疾病的复发率（RR）为 24.8%，II-III 期疾病的 RR 为 41.6%。与 ERCC1 阴性患者（36.3%，P=0.014）相比，ERCC1 阳性患者的 RR 明显更低（24.3%），与 ERCC1 C8092A 位点 AA/CA 基因型患者相比，CC 基因型患者的 RR 更高（42.1%，P=0.034）。中位无病生存（DFS）时间为 62.3 个月。与 ERCC1 阴性患者（48.0 个月，P=0.042）相比，ERCC1 阳性患者的 DFS 时间显著更长（62.3 个月）。在多变量分析中，ERCC1 表达和 C8092A 多态性是未接受化疗的 I 期疾病患者的独立预后因素。