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

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.

Novel urinary biomarkers for the detection of bladder cancer: A systematic review

“…Amplified in breast cancer 1 (AIB1) which has been shown to promote cell proliferation via AKT pathway had a sensitivity and specificity of 80% and 86% respectively 62 . When combined with eukaryotic initiation factor 2 (EIF5A2) and nuclear matrix protein (NMP22) this increased to a sensitivity of 89%, specificity of 91% and ROC of 0.898 18 . Other reports on single protein biomarkers include apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1), apolipoprotein A-I (Apo-A1), calprotectin, and NMP52 reporting sensitivity and specificity ranging from 82-94% and 80-93% respectively 11,15,17,20 .…”

“…Bladder cancer is the eight most common cancer and ranks 13 th in terms of cancer associated mortality 1 . Haematuria, a cardinal symptom for bladder cancer, has a positive predictive value of 8% and this rises to as high as 18.7% in men ≥ 70 years 2 . Patients presenting with haematuria undergo investigations including cystoscopy and upper tract imaging.…”

The Role of Novel Bladder Cancer Diagnostic and Surveillance Biomarkers—What Should a Urologist Really Know?

“…Onsidering cellular signaling proteins such as Orsomucoid-1 (acute-phase protein [ 37 ]), Osteonectin, BM40 or Secreted Protein Acidic and Rich in Cystein (SPARC—Extracellular matrix protein that promotes cellular adhesion [ 38 ]), Apurinic/apyrimidinic endonuclease 1/redox factor-1 (DNA repair and activation of transcriptional factors [ 39 ]), soluble Fas (programmed cellular death via Fas/APO-1/CD95 [ 40 ]), Aurora kinase A (AURKA—Assembly of mitotic spindle and facilitation of the mitosis [ 41 ]), Serum Irisin , (activator of gene promoters for the browning of the white adipose tissue [ 42 ]), Amplified in breast cancer 1 (AIB1—Transcriptional activity [ 43 ]) in combination with EIF5A2 (protein synthesis and in translation elongation [ 44 ]), when employed as a diagnostic biomarkers yielded variable sensitivities and specificities, ranging from 39% to 93% and 70% to 94%, respectively [ 45 , 46 ]. Although outperforming urine cytology when it comes to sensitivity, some were largely influenced by the presence of hematuria, or did not achieve satisfactory NPV to be considered for the everyday practice use.…”

Advances in Diagnosis and Therapy for Bladder Cancer

“…Over-expression of eukaryotic initiation factor 5A2 (EIF5A2) and the AIB1 gene is associated with postoperative recurrence of BCa [67]. Chen et al developed a combined EIF5A2, AIB1, and NMP22 assay model with a sensitivity and specificity of 92%, which is superior to single biomarker assays [68].…”