UBE2C cell-free RNA in urine can discriminate between bladder cancer and hematuria

Oncotarget. 2016 Sep 6;7(36):58193-58202. doi: 10.18632/oncotarget.11277.

Abstract

Background: There is growing interest in circulating nucleic acids as cancer detection biomarkers. Therefore, the aim of the present study was to identify a key urinary cell-free RNA marker that may assist in the diagnosis of BC.

Results: Five cell-free RNAs were selected as candidate cell-free RNAs from tissue microarray data. An area under the curve (AUC) cut-off value of 0.7 in receiver operating characteristic (ROC) curve analysis identified four urinary cell-free RNAs for further analysis (CDC20, ESM1, UBE2C, and CA9; AUC = 0.716, 0.704, 0.721, and 0.702, respectively). Binary logistic regression analysis revealed that high expression of UBE2C was significantly associated with BC (OR, 1.754; CI, 1.147-2.682; p = 0.010). Analysis of UBE2C expression in urine samples from BC patients and hematuria controls yielded an AUC of 0.839, with a sensitivity of 82.5% and a specificity of 76.2%. UBE2C levels was significantly increased in G2 and G3 tumors compared to normal controls (p <0.001, respectively).

Materials and methods: Urine samples from 212 BC patients and 106 normal controls (64 healthy individuals and 42 with hematuria) were examined. The candidate cell-free RNAs identified from tissue microarrays derived from BC and normal control tissues was then measured in the urine samples.

Conclusions: The levels of urinary UBE2C cell-free RNA were significantly higher in BC samples than in normal and hematuria control samples. The higher levels of urinary UBE2C cell-free RNA in BC might reflect high expression in BC tissues. Therefore, urinary UBE2C cell-free RNA may be a valuable diagnostic marker for BC.

Keywords: RNA; biomarkers; urinary bladder neoplasms; urine.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Aged
  • Area Under Curve
  • Biomarkers, Tumor / urine
  • Cell-Free Nucleic Acids / isolation & purification
  • Cell-Free Nucleic Acids / urine*
  • Early Detection of Cancer / methods
  • Female
  • Fluorescent Dyes
  • Hematuria / urine*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • RNA / isolation & purification
  • RNA / urine*
  • ROC Curve
  • Ubiquitin-Conjugating Enzymes / genetics*
  • Ubiquitin-Conjugating Enzymes / metabolism
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms / diagnosis
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / urine*

Substances

  • Biomarkers, Tumor
  • Cell-Free Nucleic Acids
  • Fluorescent Dyes
  • RNA
  • UBE2C protein, human
  • Ubiquitin-Conjugating Enzymes