DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer
DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer
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DOI：
10.1056/nejmoa065411
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发表时间：
2007-02-22
影响因子：
158.5
通讯作者：
Bepler, Gerold
中科院分区：
文献类型：
--
作者：
Zheng, Zhong;Chen, Tingan;Bepler, Gerold
背景资料：RRM 1，核糖核苷酸还原酶的调节亚基，参与致癌，肿瘤进展，和非小细胞肺癌的反应treatment.Methods：我们开发了一种自动化定量测定RRM 1蛋白在常规处理的组织学标本。在这些标本中，我们测量了RRM 1和其他两种与非小细胞肺癌相关的蛋白质的表达：切除修复交叉互补组1（ERCC 1）蛋白和磷酸酶和张力蛋白同源物（PTEN）。结果：RRM 1表达与ERCC 1表达相关（P < 0.001），与PTEN表达无相关性（P=0.37）; RRM 1高表达肿瘤患者组的中位无病生存期超过120个月，RRM 1低表达组的中位无病生存期为54.5个月（高表达组疾病进展或死亡的风险比为0.46; P=0.004）。RRM 1高表达患者的总生存期超过120个月，RRM 1低表达患者的总生存期超过60.2个月（死亡风险比为0.61; P=0.02）。在这187例患者中，RRM 1和ERCC 1同时高表达的患者仅占30%。结论：RRM 1和ERCC 1是早期非小细胞肺癌手术治疗后生存的决定因素。
Background: RRM1, the regulatory subunit of ribonucleotide reductase, is involved in carcinogenesis, tumor progression, and the response of non-small-cell lung cancer to treatment.Methods: We developed an automated quantitative determination of the RRM1 protein in routinely processed histologic specimens. In these specimens, we measured the expression of RRM1 and two other proteins that are relevant to non-small-cell lung cancer: the excision repair cross-complementation group 1 (ERCC1) protein and the phosphatase and tensin homologue (PTEN). We compared the results with the clinical outcomes in 187 patients with early-stage non-small-cell lung cancer who had received only surgical treatment.Results: RRM1 expression correlated with the expression of ERCC1 (P < 0.001) but not with the expression of PTEN (P=0.37). The median disease-free survival exceeded 120 months in the group of patients with tumors that had high expression of RRM1 and was 54.5 months in the group with low expression of RRM1 (hazard ratio for disease progression or death in the high-expression group, 0.46; P=0.004). The overall survival was more than 120 months for patients with tumors with high expression of RRM1 and 60.2 months for those with low expression of RRM1 (hazard ratio for death, 0.61; P=0.02). Among these 187 patients, the survival advantage was limited to the 30% of patients with tumors that had a high expression of both RRM1 and ERCC1.Conclusions: RRM1 and ERCC1 are determinants of survival after surgical treatment of early-stage, non-small-cell lung cancer.