Measurement of Urinary Level of a Specific Competing endogenous RNA network (FOS and RCAN mRNA/ miR-324-5p, miR-4738-3p, /lncRNA miR-497-HG) Enables Diagnosis of Bladder Cancer

Abstract

Objective: To assist in the diagnosis, treatment, and prognostic prediction of bladder cancer, the molecular patterns associated with it should be elucidated. Competing endogenous RNA network: MicroRNA (miRNA), long noncoding RNA (lncRNA), and their target autophagy genes have been strongly implicated in tumor development and metastasis.

Patients and methods: Bioinformatics analysis was performed to retrieve a ceRNA: lncRNA-miRNA-mRNA network linked to autophagy and relevant to bladder cancer. Expression of selected noncoding human RNAs (miR-324-5p, miR-4738-3p, and lncRNA miR-497-HG) and their target genes (RCAN1 mRNA and FOSB mRNA) was examined by qPCR in bladder tissues and urine samples obtained from 196 individuals (98 patients with bladder cancer, 48 patients with benign lesions, and 50 healthy controls).

Results: Expression levels of the selected genes in urine samples in the bladder cancer group were significantly different from those in the control group (P < 0.001). Expression in bladder cancer tissue samples correlated with that in urine samples. Urinary expression levels of all biomarkers had high accuracy to distinguish patients with and without bladder cancer, with FOSB mRNA and RCAN1 mRNA having the highest accuracy (99% for RCAN1 mRNA or FOSB mRNA, 87.8% for miR-324-5p, 84.7% for miR-4738-3p, and 90.5% for lncRNA miR-497-HG). FOSB mRNA and RCAN1 mRNA expression showed also a higher accuracy than cytology (77.6%).

Conclusion: The significant differential expression of the ceRNA network: lncRNA-miRNA-mRNA network in bladder cancer as compared to noncancerous controls has revealed the superior accuracy of the chosen biomarkers to cytology, especially FOSB mRNA and RCAN1 mRNA, suggesting their involvement in bladder cancer pathogenesis and promising role for future diagnosis, and targeted therapy.

Keywords: Autophagy; Bladder cancer; Noncoding RNA; Urinary biomarkers; Urine cytology.