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

尿液挥发性有机化合物作为膀胱癌新型诊断和监测生物标志物的研究

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作者:Lauren Lett #, Michael George #, Rachael Slater, Ben De Lacy Costello, Norman Ratcliffe, Marta García-Fiñana, Henry Lazarowicz, Chris Probert

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.

Conclusions

Urinary VOC analysis could aid the diagnosis and surveillance of UBC.

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.

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