Prognostic value of a microRNA signature in nasopharyngeal carcinoma: a microRNA expression analysis
Prognostic value of a microRNA signature in nasopharyngeal carcinoma: a microRNA expression analysis
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鼻咽癌中 microRNA 特征的预后价值：microRNA 表达分析
DOI：
10.1016/s1470-2045(12)70102-x
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发表时间：
2012-06-01
期刊：
影响因子：
51.1
通讯作者：
Ma, Jun
中科院分区：
文献类型：
--
作者：
Liu, Na;Chen, Nian-Yong;Ma, Jun
背景microRNA（miRNAs）可用作多种类型癌症的预后生物标志物。方法回顾性分析中山大学附属肿瘤防治中心312例鼻咽癌石蜡包埋标本和18例非癌性鼻咽炎标本中miRNA的表达谱。使用873探针微阵列，我们在随机选择的156个样本（训练集）中评估了miRNA签名与临床结果之间的关联，并在剩余的156个样本（内部验证集）中验证了结果。我们使用定量RT-PCR分析从312个样本的第二次随机化中的156个样本中确认了miRNA签名，并在中国成都四川大学华西医院的153个样本中验证了miRNA签名（独立集）。我们使用Kaplan-Meier方法和log-rank检验来估计miRNA签名与无病生存期（DFS）、无远处转移生存期（DMFS）和总生存期的相关性。在训练集中鉴定了五种miRNAs的特征，每种miRNAs均与DFS显著相关。我们根据签名计算风险评分，并将患者分为高风险或低风险。与低风险评分患者相比，训练集中高风险评分患者的DFS（风险比[HR] 2.73，95% CI 1.46-5.11; p=0.0019）、DMFS（3.48，1.57-7.75; p=0.0020）和总生存期（2.48，1.24-4.96; p=0.010）较短。我们在DFS的内部验证集中注意到了相同的发现（2.47，1.32-4.61; p=0.0052），DMFS（2.28，1.09-4.80; p=0.030），总生存期（2.87，1.38-5.96; p=0.0051）和DFS独立集中（3.16，1.65-6.04; p=0.0011）、DMFS（2.39，1.05-5.42; p=0.037）和总生存期（3.07，1.34-7.01; p=0.0082）。5-miRNA标记是独立的预后因素。在训练集中，这种特征和TNM分期的组合比单独的TNM分期具有更好的预后价值（受试者操作特征下面积0.68 [95% CI 0.60-0.76] vs 0.60 [0.52-0.67]; p=0.013），内部验证集（0.70 [0.61-0.78] vs 0.61 [0.54-0.68]; p=0.012），独立集（0.70 [0.62-0.78] vs 0.63 [0.56-0.69]; p=0.032）。解释识别具有五种-miRNA标记可能增加TNM分期系统的预后价值，并为高进展风险患者的治疗决策提供信息。
Background MicroRNAs (miRNAs) can be used as prognostic biomarkers in many types of cancer. We aimed to identify miRNAs that were prognostic in patients with nasopharyngeal carcinoma.Methods We retrospectively analysed miRNA expression profiles in 312 paraffin-embedded specimens of nasopharyngeal carcinoma from Sun Yat-sen University Cancer Center (Guangzhou, China) and 18 specimens of non-cancer nasopharyngitis. Using an 873 probe microarray, we assessed associations between miRNA signatures and clinical outcome in a randomly selected 156 samples (training set) and validated findings in the remaining 156 samples (internal validation set). We confirmed the miRNAs signature using quantitative RT-PCR analysis in 156 samples from a second randomisation of the 312 samples, and validated the miRNA signature in 153 samples from the West China Hospital of Sichuan University in Chengdu, China (independent set). We used the Kaplan-Meier method and log-rank tests to estimate correlations of the miRNA signature with disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival.Findings 41 miRNAs were differentially expressed between nasopharyngeal carcinoma and non-cancer nasopharyngitis tissues. A signature of five miRNAs, each significantly associated with DFS, was identified in the training set. We calculated a risk score from the signature and classified patients as high risk or low risk. Compared with patients with low-risk scores, patients with high risk scores in the training set had shorter DFS (hazard ratio [HR] 2.73, 95% CI 1.46-5.11; p=0.0019), DMFS (3.48, 1.57-7.75; p=0.0020), and overall survival (2.48, 1.24-4.96; p=0.010). We noted equivalent findings in the internal validation set for DFS (2.47, 1.32-4.61; p=0.0052), DMFS (2.28, 1.09-4.80; p=0.030), and overall survival (2.87, 1.38-5.96; p=0.0051) and in the independent set for DFS (3.16, 1.65-6.04; p=0.0011), DMFS (2.39, 1.05-5.42; p=0.037), and overall survival (3.07, 1.34-7.01; p=0.0082). The five-miRNA signature was an independent prognostic factor. A combination of this signature and TNM stage had better prognostic value than did TNM stage alone in the training set (area under receiver operating characteristics 0.68 [95% CI 0.60-0.76] vs 0.60 [0.52-0.67]; p=0.013), the internal validation set (0.70 [0.61-0.78] vs 0.61 [0.54-0.68]; p=0.012), and the independent set (0.70 [0.62-0.78] vs 0.63 [0.56-0.69]; p=0.032).Interpretation Identification of patients with the five-miRNA signature might add prognostic value to the TNM staging system and inform treatment decisions for patients at high risk of progression.