A four-miRNA signature identified from genome-wide serum miRNA profiling predicts survival in patients with nasopharyngeal carcinoma

摘要

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.