Detection of expression of microRNAs in serum of loco-regionally advanced nasopharyngeal carcinoma patients: A potential marker for prognosis prediction of nasopharyngeal carcinoma treated with concurrent chemoradiotherapy screening
Abstract Background Serum miRNA signature has recently been found as potential disease fingerprints to predict survival. Therefore we investigated the role of serum miRNA in predicting prognosis in patients with loco-regionally advanced nasopharyngeal carcinoma (NPC) treated with concurrent chemoradiotherapy (CCRT). Methods This study included two phases: (i) We enrolled 3 NPC patients with recurrence or distant metastasis (experimental group, EG) and 3 NPC patients in clinical remission (control group, CG), who were treated with CCRT within 5 years. The paired serum was collected before and after treatment and biomarkers were discovered by TaqMan Human MiRNA Arrays. (ii) we used the bioinformatic analysis, marker selection and an independent validation by qRT-PCR to analyse the serums of 29 NPC patients with recurrent disease or distant metastasis and 19 NPC patients treated with CCRT. We used the Kaplan-Meier method, log-rank test and Cox regression model to estimate the accuracy of the miRNAs to predict PFS and OS, and identified factors significantly associated with prognosis, respectively. Results Using fold change≥2.0 or ≤0.5 and p≤0.05 as a cutoff level, we identified 1 up-regulated and 9 down-regulated miRNAs, 1 up-regulated and 6 down-regulated miRNAs in EG versus CG before and after CCRT, respectively. After significantly down-regulated miRNA from EG versus CG before and after CCRT were removed, only 9 different miRNAs were significantly reduced. In an independent set of serum samples, the expression of miR-26b, miR-29a and miR-125b showed no significant difference in 48 NPC patients before CCRT. The expression of miR-143 and miR-29b showed no significantly difference between the two groups after CCRT. We calculated a risk score from the expression of miR-26b、miR-29a、miR-125b、miR-29b、miR-143 and then classified patients as with high or low risk. Compared to patients with low-risk score, high-risk patients had shorter PFS and OS. Cox regression model suggested that combining serum miR-29a and miR-125b before CCRT with miR-26b after CCRT was independent prognostic factors for PFS, whereas combining the former two is independent for OS. Conclusions Combined expression of serum miR-29a, miR-125b and miR-26b might provide prognostic value in loco-regionally advanced NPC patients treated with CCRT, especially for high-risk progression patients.