ERCC1, RRM1 and BRCA1 mRNA expression levels and clinical outcome of advanced non-small cell lung cancer
ERCC1, RRM1 and BRCA1 mRNA expression levels and clinical outcome of advanced non-small cell lung cancer
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晚期非小细胞肺癌ERCC1、RRM1、BRCA1 mRNA表达水平与临床转归
DOI：
10.1007/s12032-010-9553-9
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发表时间：
2011-12-01
期刊：
影响因子：
3.4
通讯作者：
Zhou, Caicun
中科院分区：
文献类型：
--
作者：
Su, Chunxia;Zhou, Songwen;Zhou, Caicun
本研究旨在探讨DNA修复基因ERCC1（切除修复交叉互补1）、RRM1（核糖核苷酸还原酶亚基M1）和BRCA1（乳腺癌1）的表达是否影响NSCLC患者的临床结局。 IIIb/IV 期 NSCLC 患者接受了铂类化疗。通过使用 TaqMan 探针的实时聚合酶链反应测定肿瘤中 ERCC1、BRCA1 和 RRM1 的信使 RNA 表达水平。本研究分析了这三个基因与化疗反应和总生存期的关系。 85 名患者（中位年龄 59 岁，范围 30-78 岁）参与了这项研究。中位总生存期 (OS) 为 13 个月（范围 10.8–15.2）。进展时间 (TTP) 为 6.1 个月（范围 5.5–6.7）。 ERCC1 表达低的患者从含铂方案中获益更多 (P= 0.094)。 RRM1 表达低的患者从含吉西他滨的治疗方案中获益更多。 BRCA1 高表达的患者从含抗微管蛋白的治疗方案中获益更多 (P= 0.046)。部分缓解率为 42.4%。与 ERCC1 水平高的患者相比，ERCC1 水平低的患者的 OS 存在统计学上的显着差异。 （16.5 个月与 10.0 个月，P= 0.045）。 ERCC1 和 BRCA1 的表达与 TTP 之间存在显着相关性（分别为 6.5 个月与 5.1 个月，P=0.001、5.2 个月与 6.5，P=0.019）。 BRCA1 的高表达与含抗微管蛋白治疗方案亚组的更好生存相关（8.7 vs. 13.0，P = 0.035）。 ERCC1、RRM1 和 BRCA1 是晚期非小细胞肺癌有希望的预测和预后生物标志物。
This study was to investigate whether the expressions of DNA repair genes ERCC1 (excision repair cross complementing 1), RRM1 (ribonucleotide reductase subunit M1) and BRCA1 (breast cancer 1) affected clinical outcome in patients with NSCLC. Patients with stage IIIb/IV NSCLC were given platinum-based chemotherapy. Messenger RNA expression levels of ERCC1, BRCA1 and RRM1 were determined by real-time polymerase chain reaction with TaqMan probes in the tumor. The relationship between these three genes with chemoresponse and overall survival was analyzed in this study. Eighty-five patients (median age 59, range 30–78) were enrolled into the study. Median overall survival (OS) was 13 months (range 10.8–15.2). Time to progression (TTP) was 6.1 months (range 5.5–6.7). Patients with low ERCC1 expression benefited more from a platinum-containing regimen (P= 0.094). Patients with low RRM1 expression benefited more from a gemcitabine-containing regimen. Patients with high BRCA1 expression benefited more from an anti-tubulin-containing regimen (P= 0.046). Partial response rate was 42.4%. A statistically significant difference in OS was seen in patients with low ERCC1 levels compared to patients with high ERCC1 ones. (16.5 vs. 10.0 months,P= 0.045). A significant relationship was observed between the expression of ERCC1 and BRCA1 and TTP (6.5 vs. 5.1 months,P= 0.001, 5.2 vs. 6.5,P= 0.019, respectively). High expression of BRCA1 was associated with better survival in the anti-tubulin-containing regimen subgroup (8.7 vs. 13.0,P= 0.035). ERCC1, RRM1 and BRCA1 are promising predictive and prognostic biomarkers in advanced non-small cell lung cancer.