Urinary exosomal long noncoding RNAs may be novel biomarkers for the diagnosis of clear cell renal cell carcinoma

Background: Renal cell carcinoma, which presents no significant clinical manifestations at early stages, is one of the few tumors with an increasing worldwide incidence. This malignancy cannot be directly detected by tumor markers in body fluid without information from imaging examinations. Approximately 30–40% of patients with kidney cancer exhibit distant metastasis at diagnosis, and their 5-year survival rate is much lower than that of patients with early-stage renal cell carcinoma. Thus, the early diagnosis of renal cell carcinoma is extremely important. The aim of this study was to investigate the utility of urinary exosomal long noncoding RNA (lncRNA) as a new potential diagnostic marker for renal cell carcinoma. Methods: Exosomes were isolated by ultracentrifugation from 50-ml urine samples from 10 patients with clear cell renal cell carcinoma and 10 matched healthy donors. Differentially expressed lncRNAs were analyzed by next-generation sequencing and further validated in kidney cancer cell lines, tissues and urinary exosomes. Then, we evaluated the sensitivity, specificity, clinical diagnostic value and stability of the selected lncRNAs. Results: The levels of lncRNAs NR_040448 and NR_033390 in urinary exosomes can likely indicate the presence of renal cell carcinoma. In addition, RNA protected by exosomes was stable enough to serve as a biomarker. Conclusion: Urinary exosomal lncRNA is a promising marker for the early diagnosis of renal cell carcinoma. Exosomes were isolated by ultracentrifugation from 50-ml urine samples from 10 patients with clear cell renal cell carcinoma and 10 matched healthy donors. Differentially expressed lncRNAs were analyzed by next-generation sequencing.