MicroRNA expression and clinical outcomes in patients treated with adjuvant chemotherapy after complete resection of non-small cell lung carcinoma.
MicroRNA expression and clinical outcomes in patients treated with adjuvant chemotherapy after complete resection of non-small cell lung carcinoma.
复制标题
DOI：
10.1158/0008-5472.can-10-1348
复制
发表时间：
2010-11-01
期刊：
影响因子：
11.2
通讯作者：
Giaccone G
中科院分区：
文献类型：
--
作者：
Voortman J;Goto A;Mendiboure J;Sohn JJ;Schetter AJ;Saito M;Dunant A;Pham TC;Petrini I;Lee A;Khan MA;Hainaut P;Pignon JP;Brambilla E;Popper HH;Filipits M;Harris CC;Giaccone G
本研究确定了一组生物学相关的 microRNA 的表达水平是否可以用作参加国际肺癌辅助试验 (IALT) 的患者的预后或预测生物标志物，这是迄今为止针对根治性切除的非小细胞肺癌 (NSCLC) 患者进行辅助化疗的最大随机研究。通过实时定量 PCR 测定 639 名 IALT 患者的石蜡包埋福尔马林固定肿瘤标本中 miR-21、miR-29b、miR-34a/b/c、miR-155 和 let-7a 的表达。使用Cox模型研究了microRNA表达对生存的预后和预测价值，该模型包括分层随机化中使用的每个因素、临床病理预后因素以及与microRNA表达统计相关的其他因素。对 microRNA 原位表达模式进行了研究。我们还分别分析了 TP53 突变状态与 miR-34a/b/c 表达、EGFR 和 KRAS 突变状态与 miR-21 和 Let-7a 表达的关联。最后，评估了 p16 和 miR-29b 表达的关联。总体而言，除 miR-21 外，任何测试的 microRNA 与生存率之间均未发现显着关联，其中表明表达降低会产生有害的预后影响。除此之外，没有单一或组合的 microRNA 表达谱预测对基于顺铂的辅助化疗的反应。总之，我们的结果表明，在随机接受基于顺铂的辅助化疗与仅接受随访的大量根治性切除 NSCLC 患者队列中，检查的 miRNA 表达模式既不能预测也不能预测预后。
This study determined whether expression levels of a panel of biologically relevant microRNAs can be used as prognostic or predictive biomarkers in patients who participated in the International Adjuvant Lung Cancer Trial (IALT), the largest randomized study conducted to date of adjuvant chemotherapy in patients with radically resected non-small cell lung carcinoma (NSCLC). Expression of miR-21, miR-29b, miR-34a/b/c, miR-155 and let-7a was determined by quantitative real-time PCR in paraffin embedded formalin fixed tumor specimens from 639 IALT patients. Prognostic and predictive value of microRNA expression for survival were studied using a Cox model, which included every factor used in the stratified randomization, clinicopathological prognostic factors and other factors statistically related to microRNA expression. Investigation of the expression pattern of microRNAs in situ was performed. We also analyzed association of TP53 mutation status and miR-34a/b/c expression, EGFR and KRAS mutation status and miR-21 and Let-7a expression, respectively. Finally, association of p16 and miR-29b expression was assessed. Overall, no significant association was found between any of the tested microRNAs and survival, with the exception of miR-21 where a deleterious prognostic effect of lowered expression was suggested. Otherwise, no single or combinatorial microRNA expression profile predicted response to adjuvant cisplatin-based chemotherapy. Together, our results indicate that the miRNA expression patterns examined were neither predictive nor prognostic in a large patient cohort of radically resected NSCLC randomized to receive adjuvant cisplatin-based chemotherapy versus follow-up only.