Clinical features and predictive biomarkers for bladder cancer in patients with type 2 diabetes presenting with haematuria

• Published in: Diabetes/metabolism research and reviews Vol. 38; no. 6; pp. e3546 - n/a
• Main Authors: Tonry, Claire L., Evans, Raymond M., Ruddock, Mark W., Duggan, Brian, McCloskey, Oonagh, Maxwell, Alexander P., O’Rourke, Declan, Boyd, Ruth E., Watt, Joanne, Reid, Cherith N., Curry, David J., Stevenson, Michael, Young, Margaret K., Jamison, Catherine S., Gallagher, Joe, Fitzgerald, Stephen P., Lamont, John, Watson, Chris J.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.09.2022
• Subjects: Biochips; Biomarkers; Biomarkers, Tumor; Bladder cancer; bladder disease; Cytokeratin; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Hematuria; Hematuria - diagnosis; Hematuria - etiology; Humans; Interleukin 6; Kidney diseases; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Monocytes; Patients; protein analysis; Proteins; Renal Insufficiency, Chronic - complications; screening; type 2; Urinary Bladder Neoplasms - complications; Urinary Bladder Neoplasms - diagnosis; Urinary Bladder Neoplasms - pathology; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A; bladder disease; screening; type 2; biomarkers; protein analysis
• ISSN: 1520-7552; 1520-7560
• DOI: 10.1002/dmrr.3546

Aims To identify clinical features and protein biomarkers associated with bladder cancer (BC) in individuals with type 2 diabetes mellitus presenting with haematuria. Materials and Methods Data collected from the Haematuria Biomarker (HaBio) study was used in this analysis. A matched sub‐cohort of patients with type 2 diabetes and patients without diabetes was created based on age, sex, and BC diagnosis, using approximately a 1:2 fixed ratio. Randox Biochip Array Technology and ELISA were applied for measurement of 66 candidate serum and urine protein biomarkers. Hazard ratios and 95% confidence intervals were estimated by chi‐squared and Wilcoxon rank sum test for clinical features and candidate protein biomarkers. Diagnostic protein biomarker models were identified using Lasso‐based binominal regression analysis. Results There was no difference in BC grade, stage, and severity between individuals with type 2 diabetes and matched controls. Incidence of chronic kidney disease (CKD) was significantly higher in patients with type 2 diabetes (p = 0.008), and CKD was significantly associated with BC in patients with type 2 diabetes (p = 0.032). A biomarker model, incorporating two serum (monocyte chemoattractant protein 1 and vascular endothelial growth factor) and three urine (interleukin 6, cytokeratin 18, and cytokeratin 8) proteins, predicted incidence of BC with an Area Under the Curve (AUC) of 0.84 in individuals with type 2 diabetes. In people without diabetes, the AUC was 0.66. Conclusions We demonstrate the potential clinical utility of a biomarker panel, which includes proteins related to BC pathogenesis and type 2 diabetes, for monitoring risk of BC in patients with type 2 diabetes. Earlier urology referral of patients with type 2 diabetes will improve outcomes for these patients. TRIAL REGISTRATION: http://www.isrctn.com/ISRCTN25823942.