Prognostic value of a microRNA signature in nasopharyngeal carcinoma: a microRNA expression analysis
The Lancet Oncology, 05/04/2012
Liu N et al. – 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.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.
- 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).