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.
Highlights
Bladder cancer (BCa) is responsible for approximately 250,000 deaths per year worldwide and is diagnosed in approximately 900,000 men and women each year [1]
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)
We constructed an enzyme-linked immunosorbent assay (ELISA) assay for AIB1, EIF5A2, and nuclear matrix protein 22 (NMP22)
Summary
Bladder cancer (BCa) is responsible for approximately 250,000 deaths per year worldwide and is diagnosed in approximately 900,000 men and women each year [1]. Accurate noninvasive detection and monitoring of BCa remains a challenge. Only NMP22 has been approved for BCa screening in patients with hematuria. None of these assays alone is sufficient for diagnosing or following BCa in clinical practice. Numerous promising single biomarkers for detecting BCa, including carcinoembryonic antigen– related cell adhesion molecule 1 (CEACAM1) [3], tumor-associated trypsin inhibitor (TATI) [4], vascular endothelial growth factor (VEGF) [5], and SERPINA1 [6], have been investigated. The ideal biomarker should be urine-based, sensitive, specific, and cost-effective, but these markers all lack one or more of these qualities
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