Serum microRNA expression signatures identified from genome-wide microRNA profiling serve as novel noninvasive biomarkers for diagnosis and recurrence of bladder cancer

Recent advantages of serum microRNAs (miRNAs) open a new realm of possibilities for noninvasive diagnosis and prognosis of bladder cancer (BC). The aim of our study was to identify serum miRNA expression signatures in patients with BC and establish new models for the diagnosis of BC and recurrence prediction. We performed genome-wide serum miRNA analysis by Miseq sequencing followed by evaluations in the training and validation sets with reverse transcription quantitative real-time PCR assays from serum samples of 250 patients with BC and 240 controls. A six-miRNA panel (miR-152, miR-148b-3p, miR-3187-3p, miR-15b-5p, miR-27a-3p and miR-30a-5p) for the diagnosis of BC was finally developed by multivariate logistic regression model with an area under the receiver operating characteristic curve of 0.899. The corresponding sensitivities of this panel for Ta, T1 and T2-T4 were 90.00, 84.85 and 89.36%, significantly higher than those of urine cytology, which were 13.33, 30.30 and 44.68%, respectively (all at p<0.001). In addition, Kaplan-Meier analysis showed that patients with nonmuscle-invasive BC (NMIBC) with high miR-152 level and low miR-3187-3p level had worse recurrence-free survival (p=0.023 and 0.043, respectively). In multivariate Cox regression analysis, miR-152 was independently associated with tumor recurrence of NMIBC (p=0.028). Our results suggested that a serum miRNA signature may have considerable clinical value in diagnosing BC. Furthermore, expression level of serum miR-152 could provide information on the recurrence risk of NMIBC. What's new? Early diagnosis can improve survival for patients with bladder cancer, but biomarkers and noninvasive tests that are sensitive enough to detect bladder tumors, and low-grade lesions in particular, are lacking. Here, following genome-wide serum miRNA analysis by Miseq sequencing in bladder cancer patients, a six-miRNA panel for diagnosis was developed. The panel was based on a multivariate logistic regression model and showed higher sensitivity than urine cytology in bladder cancer diagnosis, especially for patients with early stage disease. Among the six miRNAs identified for the panel, miR-152 was found to independently predict recurrence in non-muscle-invasive bladder cancer.