Investigation of urinary volatile organic compounds as novel diagnostic and surveillance biomarkers of bladder cancer.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
19
10
2021
accepted:
08
03
2022
revised:
21
02
2022
pubmed:
31
3
2022
medline:
22
7
2022
entrez:
30
3
2022
Statut:
ppublish
Résumé
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. 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. 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 Urinary VOC analysis could aid the diagnosis and surveillance of UBC.
Sections du résumé
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
CONCLUSIONS
Urinary VOC analysis could aid the diagnosis and surveillance of UBC.
Identifiants
pubmed: 35352020
doi: 10.1038/s41416-022-01785-8
pii: 10.1038/s41416-022-01785-8
pmc: PMC9296481
doi:
Substances chimiques
Biomarkers
0
Biomarkers, Tumor
0
Volatile Organic Compounds
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
329-336Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. The Author(s).
Références
Gorin MA, Ayyathurai R, Soloway MS. Diagnosis and treatment of bladder cancer: how can we improve? Postgrad Med. 2012;124:28–36.
doi: 10.3810/pgm.2012.05.2545
Ouzaid I, Panthier F, Hermieu JF, Xylinas E. Contemporary surgical and technical aspects of transurethral resection of bladder tumor. Transl Androl Urol. 2019;8:21–4.
doi: 10.21037/tau.2019.01.04
Boustead GB, Fowler S, Swamy R, Kocklebergh R, Hounsome L. Stage, grade and pathological characteristics of bladder cancer in the UK: British Association of Urological Surgeons (BAUS) urological tumour registry. BJU Int. 2014;113:924–30.
doi: 10.1111/bju.12468
NICE. Bladder cancer: research recommendations. National Institute for Health and Care Excellence; 2015 [Available from: https://www.nice.org.uk/guidance/ng2/chapter/2-research-recommendations ]. Accessed 09/03/2021.
Heers H, Gut JM, Hegele A, Hofmann R, Boeselt T, Hattesohl A, et al. Non-invasive detection of bladder tumors through volatile organic compounds: a pilot study with an electronic nose. Anticancer Res. 2018;38:833–7.
pubmed: 29374709
Zhu S, Corsetti S, Wang Q, Li C, Huang Z, Nabi G. Optical sensory arrays for the detection of urinary bladder cancer-related volatile organic compounds. J Biophotonics. 2019;12:e201800165.
doi: 10.1002/jbio.201800165
Willis CM, Britton LE, Harris R, Wallace J, Guest CM. Volatile organic compounds as biomarkers of bladder cancer: sensitivity and specificity using trained sniffer dogs. Cancer Biomark. 2010;8:145–53.
doi: 10.3233/CBM-2011-0208
Weber CM, Cauchi M, Patel M, Bessant C, Turner C, Britton LE, et al. Evaluation of a gas sensor array and pattern recognition for the identification of bladder cancer from urine headspace. Analyst. 2011;136:359–64.
doi: 10.1039/C0AN00382D
Khalid T, White P, De Lacy Costello B, Persad R, Ewen R, Johnson E, et al. A pilot study combining a GC-sensor device with a statistical model for the identification of bladder cancer from urine headspace. PLoS ONE. 2013;8:e69602.
doi: 10.1371/journal.pone.0069602
Aggio RB, de Lacy Costello B, White P, Khalid T, Ratcliffe NM, Persad R, et al. The use of a gas chromatography-sensor system combined with advanced statistical methods, towards the diagnosis of urological malignancies. J Breath Res. 2016;10:017106.
doi: 10.1088/1752-7155/10/1/017106
Bannaga AS, Kvasnik F, Persaud K, Arasaradnam RP. Differentiating cancer types using a urine test for volatile organic compounds. J Breath Res. 2020;15:017102.
doi: 10.1088/1752-7163/abc36b
Tyagi H, Daulton E, Bannaga AS, Arasaradnam RP, Covington JA. Urinary volatiles and chemical characterisation for the non-invasive detection of prostate and bladder cancers. Biosensors. 2021;11:1.
doi: 10.3390/bios11110437
Pinto J, Carapito Â, Amaro F, Lima AR, Carvalho-Maia C, Martins MC, et al. Discovery of volatile biomarkers for bladder cancer detection and staging through urine metabolomics. Metabolites. 2021;11:4.
doi: 10.3390/metabo11040199
Cauchi M, Weber CM, Bolt BJ, Spratt PB, Bessant C, Turner DC, et al. Evaluation of gas chromatography mass spectrometry and pattern recognition for the identification of bladder cancer from urine headspace. Anal Methods. 2016;8:4037–46.
doi: 10.1039/C6AY00400H
Gao Q, Su X, Annabi MH, Schreiter BR, Prince T, Ackerman A, et al. Application of urinary volatile organic compounds (VOCs) for the diagnosis of prostate cancer. Clin Genitourin Cancer. 2019;17:183–90.
doi: 10.1016/j.clgc.2019.02.003
Khalid T, Aggio R, White P, De Lacy Costello B, Persad R, Al-Kateb H, et al. Urinary volatile organic compounds for the detection of prostate cancer. PLoS ONE. 2015;10:e0143283.
doi: 10.1371/journal.pone.0143283
Monteiro M, Moreira N, Pinto J, Pires-Luís AS, Henrique R, Jerónimo C, et al. GC-MS metabolomics-based approach for the identification of a potential VOC-biomarker panel in the urine of renal cell carcinoma patients. J Cell Mol Med. 2017;21:2092–105.
doi: 10.1111/jcmm.13132
Wang D, Wang C, Pi X, Guo L, Wang Y, Li M, et al. Urinary volatile organic compounds as potential biomarkers for renal cell carcinoma. Biomed Rep. 2016;5:68–72.
doi: 10.3892/br.2016.686
Smith S, Burden H, Persad R, Whittington K, de Lacy Costello B, Ratcliffe NM, et al. A comparative study of the analysis of human urine headspace using gas chromatography-mass spectrometry. J Breath Res. 2008;2:037022.
doi: 10.1088/1752-7155/2/3/037022
Zhang S, Raftery D. Headspace SPME-GC-MS metabolomics analysis of urinary volatile organic compounds (VOCs). Methods Mol Biol. 2014;1198:265–72.
doi: 10.1007/978-1-4939-1258-2_17
Machin D, Capmbell MJ, Tan SB, Tan SH. Reference intervals and receiver operating curves. In: Machin D, Capmbell MJ, Tan SB, Tan SH. (eds). Sample size tables for clinical studies. Third Edition edn. (Wiley-Blackwell: Chichester, West Sussex, United Kingdom, 2009) pp 158–178.
McFarlanE M, MozdiaK E, Daulton E, Arasaradnam R, Covington J, Nwokolo C. Pre-analytical and analytical variables that influence urinary volatile organic compound measurements. PLoS ONE. 2020;15:e0236591-e.
doi: 10.1371/journal.pone.0236591
Esfahani S, Sagar NM, Kyrou I, Mozdiak E, O’Connell N, Nwokolo C, et al. Variation in gas and volatile compound emissions from human urine as it ages, measured by an electronic nose. Biosens. 2016;6:1.
doi: 10.3390/bios6010004
Aggarwal P, Baker J, Boyd MT, Coyle S, Probert C, Chapman EA. Optimisation of urine sample preparation for headspace-solid phase microextraction gas chromatography-mass spectrometry: altering sample pH, sulphuric acid concentration and phase ratio. Metabolites 2020;10:12.
doi: 10.3390/metabo10120482
Drabińska N, Młynarz P, de Lacy Costello B, Jones P, Mielko K, Mielnik J, et al. An optimization of liquid-liquid extraction of urinary volatile and semi-volatile compounds and its application for gas chromatography-mass spectrometry and proton nuclear magnetic resonance spectroscopy. Molecules. 2020;25:3651.
doi: 10.3390/molecules25163651
Natalia D, Starowicz M, Krupa-Kozak U. Headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry for the determination of volatile organic compounds in urine. J Anal Chem. 2020;75:792–801.
doi: 10.1134/S1061934820060088
Aggio R, Villas-Bôas SG, Ruggiero K. Metab: an R package for high-throughput analysis of metabolomics data generated by GC-MS. Bioinformatics. 2011;27:2316–8.
doi: 10.1093/bioinformatics/btr379
Rodrigues D, Pinto J, Araújo AM, Monteiro-Reis S, Jerónimo C, Henrique R, et al. Volatile metabolomic signature of bladder cancer cell lines based on gas chromatography–mass spectrometry. Metabolomics 2018;14:62.
doi: 10.1007/s11306-018-1361-9
Janfaza S, Khorsand B, Nikkhah M, Zahiri J. Digging deeper into volatile organic compounds associated with cancer. Biol Methods Protoc. 2019;4:bpz014.
doi: 10.1093/biomethods/bpz014
Shephard EA, Stapley S, Neal RD, Rose P, Walter FM, Hamilton WT. Clinical features of bladder cancer in primary care. Br J Gen Pr. 2012;62:e598–604.
doi: 10.3399/bjgp12X654560
Chou R, Gore JL, Buckley D, Fu R, Gustafson K, Griffin JC, et al. Urinary biomarkers for diagnosis of bladder cancer: a systematic review and meta-analysis. Ann Intern Med. 2015;163:922–31.
doi: 10.7326/M15-0997
Todenhöfer T, Hennenlotter J, Esser M, Mohrhardt S, Aufderklamm S, Böttge J, et al. Stepwise application of urine markers to detect tumor recurrence in patients undergoing surveillance for non-muscle-invasive bladder cancer. Dis Markers. 2014;2014:973406.
doi: 10.1155/2014/973406
Horstmann M, Patschan O, Hennenlotter J, Senger E, Feil G, Stenzl A. Combinations of urine-based tumour markers in bladder cancer surveillance. Scand J Urol Nephrol. 2009;43:461–6.
doi: 10.3109/00365590903296837
Lima AR, Pinto J, Azevedo AI, Barros-Silva D, Jerónimo C, Henrique R, et al. Identification of a biomarker panel for improvement of prostate cancer diagnosis by volatile metabolic profiling of urine. Br J Cancer. 2019;121:857–68.
doi: 10.1038/s41416-019-0585-4