Cell-Free Rna Content In Urine As A Possible Molecular Diagnostic Tool For Clear Cell Renal Cell Carcinoma

There is limited research on cell-free RNA (cf-RNA) in the urine of cancer patients. The present study was performed to detect the cf-RNA in the urine of patients with clear cell renal cell carcinoma (ccRCC). Ninety-five urine samples from ccRCC patients and 50 urine samples from control subjects were analyzed. The cf-RNA integrity index was calculated by using quantitative real-time RT-PCR assays of the small-sized fragment (106 bp) and the big-sized fragment (416 bp) in GAPDH mRNA. The initial analysis showed that cf-RNA was stable and detectable in the urine. The mean cf-RNA integrity index was significantly lower in the urine of ccRCC patients (mean: 0.07, 95%CI: 0.05-0.10) when compared with the urine from control subjects (mean: 0.25, 95%CI: 0.16-0.33) (p<0.001). The value of the area under the receiver-operating characteristic curve by using the cf-RNA integrity index for the diagnosis of ccRCC was 0.858 with a sensitivity of 68.0% and a specificity of 92.6%. Moreover, the small-sized VEGF mRNA fragment (98 bp) was detected in 31 of 50 urine samples of patients with ccRCC and in only 2 of 50 urine samples of control subjects (p<0.001) while the detection of the big-sized (420 bp) VEGF mRNA fragment was an infrequent event. Our findings suggest that the small-sized cf-RNA in urine was more abundant in cancer patients. The tumor-related gene VEGF mRNA fragment was detectable in the urine of cancer patients. Our finding may provide a new molecular assay for the diagnosis of renal cell carcinoma.What's new? The detection of cell-free RNA (cf-RNA) in biological fluids raises possibilities for the development of new diagnostic assays for cancer. Such an assay may be applicable particularly for clear cell renal cell carcinoma (ccRCC). In this study, the urinary cf-RNA integrity index in ccRCC patients was found to be significantly reduced compared to control subjects. However, small-sized cf-RNA fragments, including small fragments (98 bp) of VEGF mRNA, were present at increased levels in the urine of cancer patients. Additional investigation is needed to confirm the findings and to define the clinical utility of cf-RNA detection for ccRCC.