马骏和陈念永教授的合作，为鼻咽癌的个体化治疗提供了重要指导。
经过3年研究，中山大学肿瘤防治中心马骏教授与四川大学华西医院陈念永教授课题组合作，发现了一个预测鼻咽癌预后的分子标签，为鼻咽癌的个体化治疗提供了重要指导。该研究论文发表在知名学术杂志《柳叶刀·肿瘤学》上。
鼻咽癌TNM临床分期系统，是鼻咽癌预后判断和指导治疗的重要依据，但研究人员很早就发现，给予同一分期患者相同的治疗方案，预后却截然不同，这提示鼻咽癌生物学差异的存在。因此，仅基于解剖学信息的TNM临床分期系统并不能十分准确预测鼻咽癌的预后。
马骏与陈念永课题组分别从中山大学肿瘤防治中心和四川大学华西医院回顾性收集了465个就诊时无远处转移的鼻咽癌患者标本，通过芯片和定量PCR检测，发现一个由5个miRNA构成的分子标签，能很好地预测鼻咽癌患者的预后，特别是远处转移。研究人员以该miRNA分子标签和TNM临床分期，联合构建了一个预后危险评分模型，发现该模型的鼻咽癌预后预测能力明显优于单纯的TNM临床分期，能更准确地筛选出高危病人。
研究人员指出，该研究有可能开辟新的临床治疗思路，先帮助临床医生早期准确筛选出常规治疗效果较差的鼻咽癌患者，并给予更高强度治疗以改善其预后。
Prognostic value of a microRNA signature in nasopharyngeal carcinoma: a microRNA expression analysis
Na Liu MD, Prof Nian-Yong Chen MD, Rui-Xue Cui MD, Wen-Fei Li MD, Yan Li MD, Rong-Rong Wei PhD, Mei-Yin Zhang MD, Ying Sun PhD, Bi-Jun Huang MD, Mo Chen MD, Qing-Mei He MD, Ning Jiang MD, Lei Chen MD, Prof William CS Cho PhD, Prof Jing-Ping Yun PhD, Jing Zeng PhD, Li-Zhi Liu MD, Prof Li Li PhD, Ying Guo PhD, Prof Hui-Yun Wang PhD, Prof Jun Ma MD
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.
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.
文献连接：Prognostic value of a microRNA signature in nasopharyngeal carcinoma: a microRNA expression analysis
