Prognostic value of a microRNA signature in nasopharyngeal carcinoma: a microRNA expression analysis

详细信息	查看全文 | 推荐本文 |

• 作者：Na Liu ; MD^a ; ^* ; Prof Nian-Yong Chen ; MD^f ; ^* ; Rui-Xue Cui ; MD^a ; ^* ; Wen-Fei Li ; MD^a ; Yan Li ; MD^f ; Rong-Rong Wei ; PhD^d ; Mei-Yin Zhang ; MD^d ; Ying Sun ; PhD^a ; Bi-Jun Huang ; MD^d ; Mo Chen ; MD^a ; Qing-Mei He ; MD^d ; Ning Jiang ; MD^a ; Lei Chen ; MD^a ; Prof William CS Cho ; PhD^g ; Prof Jing-Ping Yun ; PhD^b ; Jing Zeng ; PhD^b ; Li-Zhi Liu ; MD^c ; Prof Li Li ; PhD^c ; Ying Guo ; PhD^e ; Prof Hui-Yun Wang ; PhD^d ; ^&dagger ; ; Prof Jun Ma ; MD^a ; ^&dagger ; ; ^{majun2@mail.sysu.edu.cn}
• 刊名：Lancet Oncology
• 出版年：2012
• 期刊代码：184_14702045
• 类别：med
• 出版时间：June, 2012
• 卷：13
• 期：6
• 页码：633-641
• 文件大小：288 K

摘要

| Figures/TablesFigures/Tables | ReferencesReferences

Summary

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路73, 95%CI 1路46-5路11; p=0路0019), DMFS (3路48, 1路57-7路75; p=0路0020), and overall survival (2路48, 1路24-4路96; p=0路010). We noted equivalent findings in the internal validation set for DFS (2路47, 1路32-4路61; p=0路0052), DMFS (2路28, 1路09-4路80; p=0路030), and overall survival (2路87, 1路38-5路96; p=0路0051) and in the independent set for DFS (3路16, 1路65-6路04; p=0路0011), DMFS (2路39, 1路05-5路42; p=0路037), and overall survival (3路07, 1路34-7路01; p=0路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路68 [95%CI 0路60-0路76] vs 0路60 [0路52-0路67]; p=0路013), the internal validation set (0路70 [0路61-0路78] vs 0路61 [0路54-0路68]; p=0路012), and the independent set (0路70 [0路62-0路78] vs 0路63 [0路56-0路69]; p=0路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.

Funding

Science Foundation of Chinese Ministry of Health, National Natural Science Foundation of China, Pearl River Scholar Funded Scheme, Guangdong Key Scientific and Technological Innovation Program, Guangdong Natural Science Foundation, Fundamental Research Funds for the Central Universities.