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

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.

Recent Applications of Gas Chromatography in Bioanalysis

“…Other examples of VOCs as biomarkers determined by GC technique and their concentrations used for illness diagnostics include, for example, (i) alkanes, monomethylated alkanes for breast cancer; (ii) S-containing compounds, such as methyl mercaptan, dimethylsulfide for hepatic coma and cholera [15,26]; (iii) carbon disulfide, pentane, ethane for schizophrenia; (iv) hexanal, 1-octen-3-ol and octane for liver cancer [27]; and (v) nonanal, 2-ethylhexan-1-ol, 5-ethyl-3-methyloxolan-2-one, heptan-2-one, 1,1,4a-trimethyl-4,5,6,7-tetrahydro-3H-naphthalen-2-one and propan-2-one from urine as surveillance biomarker of bladder cancer [28].…”

A Liquid Biopsy in Bladder Cancer—The Current Landscape in Urinary Biomarkers

“…Analysis of urinary volatile organic compounds (VOCs) in a cross-sectional study [ 61 ] compared the profiles of patients with and without BCa and revealed potential signatures of diagnostic feasibility. Urine samples were collected from clinic patients with hematuria (21 had a new diagnosis of BCa, 125 had no cancer) undergoing diagnostic cystoscopy and patients with BCa undergoing follow-up (75 had recurrent BCa, 84 had no recurrence).…”

The untargeted urine volatilome for biomedical applications: methodology and volatilome database

“…The authors selected different methodologies; Hanai et al used SPME extraction identifying 19 compounds whereas Porto-Figueira et al used NTD to identify 98 compounds [ 47 , 48 ]. Bladder cancer has a direct relation with urine, Jobu et al evaluate it by NeedleEx whereas Lett et al used SPME [ 49 , 50 ]. Comparison of techniques is not possible as results are not completely disclosed.…”