Department of Oncological Intensive Care and Emergencies & Thoracic Oncology, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Lung Cancer. 2013 Nov;82(2):340-5. doi: 10.1016/j.lungcan.2013.07.020. Epub 2013 Aug 7.
Clinical variables, like stage and performance status (PS), have predictive and prognostic values in advanced non-small cell lung cancer (NSCLC) patients treated with chemotherapy, not allowing adequate individual prediction. MicroRNA (miRNA) are non-coding RNAs regulating gene expression. In a prospective study, we assessed the predictive value for response and survival of tumour miRNA in NSCLC patients treated by 1st line cisplatin and vinorelbine. miRNA expression was analysed on a biopsy obtained during the diagnostic bronchoscopy, using TaqMan Low Density Arrays. The signature for response was derived using logistic regression with stepwise variable selection. The associations between overall survival and miRNA expression levels were estimated by using the Kaplan-Meier method, log-rank test, and Cox proportional hazard regression models to estimate the hazard ratios. In total, 38 patients with adequate tumour biopsies, treated with cisplatin-vinorelbine were included: male (n = 27), 80-100 Karnofsky PS (n = 27), adenocarcinoma (n = 20), stage IV (n = 30). One patient was considered not assessable for response but remained included in the survival analyses. Out of the 37 patients assessable for response, 16 partial responses (43%) were observed. A two miRNA signature (miR-149 and miR-375) was found predictive for response and was also associated to progression-free survival (p = 0.05). Using a linear combination of the miR CT values with Cox's regression coefficients as weights, we constructed a prognostic score for overall survival including four miRNA (miR-200c, miR-424, miR-29c and miR-124). The signature distinguished patients with good (n = 18) and poor (n = 20) prognosis with respective median survival times of 47.3 months (95% CI 29.8-52.4) and 15.5 months (95% CI 9.1-22.8) (p < 0.001; hazard ratio 21.1, 95% CI 4.7-94.9).
miRNA signature allows predicting response and is of prognostic value for survival in patients with NSCLC treated with first line cisplatin and vinorelbine.
目的：评估肿瘤 miRNA 在接受一线顺铂和长春瑞滨治疗的 NSCLC 患者中的预测和生存价值。
方法：这是一项前瞻性研究，对诊断性支气管镜检查期间获得的活检标本进行 miRNA 表达分析，使用 TaqMan 低密度阵列。使用逐步变量选择的逻辑回归推导反应的特征。使用 Kaplan-Meier 方法、对数秩检验和 Cox 比例风险回归模型估计总生存与 miRNA 表达水平之间的关联，以估计风险比。
结果：共纳入 38 例接受顺铂-长春瑞滨治疗且肿瘤活检充分的患者：男性（n=27），Karnofsky PS 评分 80-100（n=27），腺癌（n=20），IV 期（n=30）。1 例患者被认为对反应不可评估，但仍纳入生存分析。在 37 例可评估反应的患者中，观察到 16 例部分缓解（43%）。发现两个 miRNA 特征（miR-149 和 miR-375）可预测反应，与无进展生存期（p=0.05）相关。使用 Cox 回归系数作为权重的 miR CT 值的线性组合，我们构建了一个包括四个 miRNA（miR-200c、miR-424、miR-29c 和 miR-124）的总体生存预后评分。该特征区分了预后良好（n=18）和预后不良（n=20）的患者，中位生存时间分别为 47.3 个月（95%CI 29.8-52.4）和 15.5 个月（95%CI 9.1-22.8）（p<0.001；危险比 21.1，95%CI 4.7-94.9）。
结论：miRNA 特征可预测反应，并且对于接受一线顺铂和长春瑞滨治疗的 NSCLC 患者的生存具有预后价值。
