吉西他滨/卡铂治疗晚期非小细胞肺癌时外周血与肿瘤组织中 RRM1 和 ERCC1 的表达。
RRM1 and ERCC1 expression in peripheral blood versus tumor tissue in gemcitabine/carboplatin-treated advanced non-small cell lung cancer.
机构信息
Department of Pharmacy, The First AYliated Hospital, School of Medicine, Zhejiang University, 79 Qing Chun Street, Hangzhou 310003, People's Republic of China.
出版信息
Cancer Chemother Pharmacol. 2012 May;69(5):1277-87. doi: 10.1007/s00280-012-1834-x.
PURPOSE
To comparatively evaluate the prognostic or predictive value of ribonucleotide reductase M1 (RRM1) and excision repair cross-complementation 1 (ERCC1) gene expression in peripheral blood versus tumor tissue from patients with advanced non-small cell lung cancer (NSCLC) treated by gemcitabine/platinum chemotherapy.
METHODS
A total of 49 patients with advanced NSCLC receiving gemcitabine plus carboplatin chemotherapy were studied. RRM1 and ERCC1 mRNA levels in the peripheral blood and tumor tissue were determined by real-time fluorescent quantitative PCR. The relationships between gene expression and clinical and pathological factors, response to chemotherapy as well as prognosis, were evaluated.
RESULTS
RRM1 expression in peripheral blood and tumor tissue, but not ERCC1 expression, was found to be positively correlated (r = 0.332, 0.258; P = 0.020, 0.073; respectively). RRM1 and ERCC1 expression levels were nearly synchronous in both peripheral blood (r = 0.351; P = 0.013) and tumor tissue (r = 0.634; P < 0.001). Neither was correlated with clinical and pathological factors.
PATIENTS
with low RRM1 expression in peripheral blood or low RRM1 or ERCC1 expression in tumor tissue experienced better response to chemotherapy (50.0 vs. 16.0%, 50.0 vs. 16.0%, and 54.2 vs. 12.0%; P = 0.012, 0.012, and 0.003; respectively), longer median survival (18.5 vs. 13.0 months, 18.5 vs. 12.0 months, and 19.8 vs. 12.5 months; P = 0.043, 0.014 and 0.007; respectively), and longer progression-free survival (6.0 vs. 4.0 months, 7.8 vs. 3.9 months, and 5.8 vs. 3.8 months; P = 0.044, 0.016, and 0.008; respectively). Cox multivariate regression analysis showed that ERCC1 expression in tumor tissue was independent indicator for overall survival.
CONCLUSIONS
Advanced NSCLC patients with low RRM1 mRNA expression both in peripheral blood and in tumor tissue could benefit from gemcitabine/carboplatin chemotherapy. ERCC1 mRNA expression in tumor tissue may be a predictive and prognostic indicator in advanced NSCLC patients receiving gemcitabine/carboplatin chemotherapy.
目的
比较评估晚期非小细胞肺癌（NSCLC）患者外周血和肿瘤组织中核苷酸还原酶 M1（RRM1）和切除修复交叉互补基因 1（ERCC1）基因表达的预后或预测价值，这些患者接受吉西他滨/铂类化疗。
方法
共对 49 例接受吉西他滨加卡铂化疗的晚期 NSCLC 患者进行了研究。采用实时荧光定量 PCR 法测定外周血和肿瘤组织中 RRM1 和 ERCC1 mRNA 水平。评估基因表达与临床和病理因素、化疗反应及预后的关系。
结果
外周血和肿瘤组织中 RRM1 的表达（但不是 ERCC1 的表达）呈正相关（r = 0.332，0.258；P = 0.020，0.073；分别）。外周血（r = 0.351；P = 0.013）和肿瘤组织（r = 0.634；P < 0.001）中 RRM1 和 ERCC1 的表达水平几乎同步。它们均与临床和病理因素无关。
患者
外周血中 RRM1 表达水平低或肿瘤组织中 RRM1 或 ERCC1 表达水平低的患者对化疗反应更好（50.0% vs. 16.0%，50.0% vs. 16.0%，54.2% vs. 12.0%；P = 0.012，0.012，0.003；分别），中位生存期更长（18.5 个月 vs. 13.0 个月，18.5 个月 vs. 12.0 个月，19.8 个月 vs. 12.5 个月；P = 0.043，0.014 和 0.007；分别），无进展生存期更长（6.0 个月 vs. 4.0 个月，7.8 个月 vs. 3.9 个月，5.8 个月 vs. 3.8 个月；P = 0.044，0.016，0.008；分别）。Cox 多变量回归分析显示，肿瘤组织中 ERCC1 的表达是总生存的独立指标。
结论
外周血和肿瘤组织中 RRM1 mRNA 表达均较低的晚期 NSCLC 患者可能从吉西他滨/卡铂化疗中获益。肿瘤组织中 ERCC1 mRNA 表达可能是接受吉西他滨/卡铂化疗的晚期 NSCLC 患者的预测和预后指标。
Zotero 插件