Identification of urinary hsa_circ_0137439 as a potential biomarker and tumor regulator of bladder cancer

Abstract

Cell-free circular RNAs (circRNAs) stably and abundantly exist in body fluids. In this study we aimed to investigate the potential of urinary cell-free circRNAs as a novel class of non-invasive disease biomarkers for diagnosis of bladder cancer. Differentially expressed circRNAs from 10 normal and 10 bladder cancer urine samples were firstly detected by microarray. Hsa_circ_0137439 was then screened and validated in 30 normal and 116 bladder cancer samples. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of hsa_circ_0137439. The Kaplan-Meier method was used to evaluate the significance of hsa_circ_0137439 in the prognosis of bladder cancer. We found that hsa_circ_0137439 was significantly upregulated in bladder cancer samples. Moreover, increased expression of hsa_circ_0137439 was correlated with higher tumor stage, higher tumor grade, higher lymph node status, and history of muscle-invasive bladder cancer (MIBC). Also, urinary cell-free hsa_circ_0137439 could not only differentiate bladder cancer from normal controls but also distinguish MIBC from non-muscle-invasive bladder cancer (NMIBC). Additionally, hsa_circ_0137439 in urine superna-tant could serve as an independent prognostic predicator of recurrence-free survival and overall survival for patients with bladder cancer. Cell assays showed that hsa_circ_0137439 knockdown contributed to the inhibition of cell proliferation and migration via hsa_circ_0137439/miR-142-5p/MTDH axis. In conclusion, urinary cell-free hsa_circ_0137439 could be a promising biomarker for tumor diagnosis and prognostic assessment of bladder cancer patients.