Investigation of urinary volatile organic compounds as novel diagnostic and surveillance biomarkers of bladder cancer

Lett, Lauren; George, Michael; Slater, Rachael; De Lacy Costello, Ben; Ratcliffe, Norman; Garc�a-Fi�ana, Marta; Lazarowicz, Henry; Probert, Chris

Abstract

Background: The diagnosis and surveillance of urothelial bladder cancer (UBC) require cystoscopy. There is a need for biomarkers to reduce the frequency of cystoscopy in surveillance; urinary volatile organic compound (VOC) analysis could fulfil this role. This cross-sectional study compared the VOC profiles of patients with and without UBC, to investigate metabolomic signatures as biomarkers. Methods: Urine samples were collected from haematuria clinic patients undergoing diagnostic cystoscopy and UBC patients undergoing surveillance. Urinary headspace sampling utilised solid-phase microextraction and VOC analysis applied gas chromatography-mass spectrometry; the output underwent metabolomic analysis. Results: The median participant age was 70 years, 66.2% were male. Of the haematuria patients, 21 had a new UBC diagnosis, 125 had no cancer. In the surveillance group, 75 had recurrent UBC, 84 were recurrence-free. A distinctive VOC profile was observed in UBC patients compared with controls. Ten VOCs had statistically significant abundances useful to classify patients (false discovery rate range 1.9 × 10−7–2.8 × 10−2). Two prediction models were evaluated using internal validation. An eight-VOC diagnostic biomarker panel achieved AUROC 0.77 (sensitivity 0.71, specificity 0.72). A six-VOC surveillance biomarker panel obtained AUROC 0.80 (sensitivity 0.71 and specificity 0.80). Conclusions: Urinary VOC analysis could aid the diagnosis and surveillance of UBC.

• Journal Article Type: Article
• Acceptance Date: Mar 8, 2022
• Online Publication Date: Mar 29, 2022
• Publication Date: Jul 20, 2022
• Deposit Date: Jul 28, 2022
• Publicly Available Date: Jul 29, 2022
• Journal: British Journal of Cancer
• Print ISSN: 0007-0920
• Electronic ISSN: 1532-1827
• Publisher: Springer Nature [academic journals on nature.com]
• Peer Reviewed: Peer Reviewed
• Volume: 127
• Issue: 2
• Pages: 329-336
• DOI: https://doi.org/10.1038/s41416-022-01785-8
• Keywords: Bladder cancer; Diagnostic markers; Molecular medicine; Predictive markers
• Public URL: https://uwe-repository.worktribe.com/output/9722880
• Publisher URL: https://www.nature.com/articles/s41416-022-01785-8