Cell-free RNA content in urine as a possible molecular diagnostic tool for clear cell renal cell carcinoma

Int J Cancer. 2015 Jun 1;136(11):2610-5. doi: 10.1002/ijc.29313. Epub 2014 Nov 28.

Abstract

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.

Keywords: Urine; cf-RNA integrity index; diagnosis; renal cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Renal Cell / diagnosis
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / urine*
  • Cell-Free System
  • Early Detection of Cancer
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms / diagnosis
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / urine*
  • Male
  • Middle Aged
  • RNA Stability
  • RNA, Neoplasm / urine*
  • Real-Time Polymerase Chain Reaction
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor A / urine

Substances

  • RNA, Neoplasm
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A