A four-miRNA signature identified from genome-wide serum miRNA profiling predicts survival in patients with nasopharyngeal carcinoma
A four-miRNA signature identified from genome-wide serum miRNA profiling predicts survival in patients with nasopharyngeal carcinoma
复制标题
从全基因组血清 miRNA 分析中鉴定出的四个 miRNA 特征可预测鼻咽癌患者的生存
DOI：
10.1002/ijc.28468
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发表时间：
2014-03-15
影响因子：
6.4
通讯作者：
Ma, Jun
中科院分区：
文献类型：
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作者：
Liu, Na;Cui, Rui-Xue;Ma, Jun
最近的研究发现，人血清microRNAs（miRNAs）可用作各种癌症的预后生物标志物。本研究旨在探讨血清miRNAs在鼻咽癌患者预后中的价值。回顾性分析2001年1月至2006年12月间512例鼻咽癌患者血清中miRNA水平。在发现阶段，使用微阵列随后进行逆转录-定量聚合酶链反应来鉴定8名生存期较短的患者和8名生存期较长的患者中差异改变的miRNA，这些患者的年龄，性别和临床分期匹配良好。然后在所有512个样本中验证鉴定的血清miRNA，这些样本被随机分为训练集和验证集。发现四种血清miRNA（miR-22、miR-572、miR-638和miR-1234）被差异改变，并用于构建miRNA签名。计算风险评分，将患者分为高风险组或低风险组。高风险评分患者的总生存率[风险比（HR），2.54; 95%可信区间（CI），1.57-4.12; p < 0.001]和无远处转移生存率较差（HR，3.28; 95%CI，1.82-5.94; p < 0.001）;这些结果在验证集和组合集中得到证实。miRNA信号和TNM分期是独立的预后因素。miRNA标签和TNM分期的组合比TNM分期或单独的miRNA标签具有更好的预后价值。四种血清miRNA标记物可能为TNM分期系统增加预后价值，并为NPC的个性化治疗提供信息。在血清中循环的短的非编码RNA序列或microRNA是容易获得的，有希望的生物标志物，用于并入肿瘤-淋巴结-转移（TNM）分期系统。这项研究表明，四个miRNA签名能够预测鼻咽癌的生存率，作为一个独立的预后因素。当与TNM分期相结合时，miRNA签名提高了整体预后能力，比单独使用任何一种方法都有所改善。结果还表明，血清miRNAs除了作为潜在的预后生物标志物外，还可能在鼻咽癌的发生和进展中发挥重要作用。
Recent findings have reported that human serum microRNAs (miRNAs) can be used as prognostic biomarkers in various cancers. We aimed to explore the prognostic value of serum miRNAs in nasopharyngeal carcinoma (NPC) patients. The level of serum miRNA was retrospectively analyzed in 512 NPC patients recruited between January 2001 and December 2006. In the discovery stage, a microarray followed by reverse transcription-quantitative polymerase chain reaction was used to identify differentially altered miRNAs in eight patients with shorter survival and eight patients with longer survival who were well matched by age, sex and clinical stage. The identified serum miRNAs were then validated in all 512 samples, which were randomly divided into a training set and a validation set. Four serum miRNAs (miR-22, miR-572, miR-638 and miR-1234) were found to be differentially altered and were used to construct a miRNA signature. Risk scores were calculated to classify the patients into high- or low-risk groups. Patients with high-risk scores had poorer overall survival [hazard ratio (HR), 2.54; 95% confidence interval (CI), 1.57-4.12; p < 0.001] and distant metastasis-free survival (HR, 3.28; 95% CI, 1.82-5.94; p < 0.001) than those with low-risk scores in the training set; these results were confirmed in the validation and combined sets. The miRNA signature and TNM stage were independent prognostic factors. The combination of the miRNA signature and TNM stage had a better prognostic value than the TNM stage or miRNA signature alone. The four-serum miRNA signature may add prognostic value to the TNM staging system and provide information for personalized therapy in NPC.What's new? Short non-coding RNA sequences, or microRNAs, that circulate in serum are easily accessible, promising biomarkers for incorporation into the tumor-node-metastasis (TNM) staging system. This study shows that a four-miRNA signature is able to predict survival in nasopharyngeal carcinoma, serving as an independent prognostic factor. When combined with TNM staging, the miRNA signature boosted the overall prognostic power, improving it over either approach alone. The results also suggest that serum miRNAs may play an important role in nasopharyngeal carcinoma development and progression, in addition to being potential prognostic biomarkers.