Identification and validation of AIB1 and EIF5A2 for noninvasive detection of bladder cancer in urine samples

Oncotarget. 2016 Jul 5;7(27):41703-41714. doi: 10.18632/oncotarget.9406.

Abstract

We previously demonstrated that amplified in breast cancer 1 (AIB1) and eukaryotic initiation factor 2 (EIF5A2) overexpression was an independent predictor of poor clinical outcomes for patients with bladder cancer (BCa). In this study, we evaluated the usefulness of AIB1 and EIF5A2 alone and in combination with nuclear matrix protein 22 (NMP22) as noninvasive diagnostic tests for BCa. Using urine samples from 135 patients (training set, controls [n = 50] and BCa [n = 85]), we detected the AIB1, EIF5A2, and NMP22 concentrations using enzyme-linked immunosorbent assay. We applied multivariate logistic regression analysis to build a model based on the three biomarkers for BCa diagnosis. The diagnostic accuracy of the three biomarkers and the model were assessed and compared by the area under the curve (AUC) of the receiver operating characteristic. We validated the diagnostic accuracy of these biomarkers and the model in an independent validation cohort of 210 patients. In the training set, urinary concentrations of AIB1, EIF5A2, and NMP22 were significantly elevated in BCa. The AUCs of AIB1, EIF5A2, NMP22, and the model were 0.846, 0.761, 0.794, and 0.919, respectively. The model had the highest diagnostic accuracy when compared with AIB1, EIF5A2, or NMP22 (p < 0.05 for all). The model had 92% sensitivity and 92% specificity. We obtained similar results in the independent validation cohort. AIB1 and EIF5A2 show promise for the noninvasive detection of BCa. The model based on AIB1, EIF5A2, and NMP22 outperformed each of the three individual biomarkers for detecting BCa.

Keywords: AIB1; EIF5A2; bladder cancer; diagnostic model; urine biomarkers.

Publication types

  • Validation Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / urine
  • Biomarkers, Tumor / urine*
  • Carcinoma, Transitional Cell / diagnosis
  • Carcinoma, Transitional Cell / pathology
  • Carcinoma, Transitional Cell / urine*
  • Cohort Studies
  • Early Detection of Cancer / methods*
  • Enzyme-Linked Immunosorbent Assay
  • Eukaryotic Translation Initiation Factor 5A
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nuclear Proteins / urine
  • Nuclear Receptor Coactivator 3 / analysis
  • Nuclear Receptor Coactivator 3 / urine*
  • Peptide Initiation Factors / analysis
  • Peptide Initiation Factors / urine*
  • Predictive Value of Tests
  • RNA-Binding Proteins / analysis
  • RNA-Binding Proteins / urine*
  • Sensitivity and Specificity
  • Urinalysis / methods
  • Urinalysis / standards
  • Urinary Bladder Neoplasms / diagnosis
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / urine*

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Nuclear Proteins
  • Peptide Initiation Factors
  • RNA-Binding Proteins
  • nuclear matrix protein 22
  • NCOA3 protein, human
  • Nuclear Receptor Coactivator 3