Volatolomic urinary profile analysis for diagnosis of the early stage of lung cancer.

ABSTRACT

Currently, in clinical practice there is a pressing need for potential biomarkers that can identify lung cancer at early stage before becoming symptomatic or detectable by conventional means. Several researchers have independently pointed out that the volatile organic compounds (VOCs) profile can be considered as a lung cancer fingerprint useful for diagnosis. In particular, 16% of volatiles contributing to the human volatilome are found in urine, which is therefore an ideal sample medium. Its analysis through non-invasive, relatively low-cost and straightforward techniques could offer great potential for the early diagnosis of lung cancer. In this study, urinary VOCs were analysed with a gas chromatography-ion mobility spectrometer (GC-IMS) and an electronic nose (e-nose) made by a matrix of twelve quartz microbalances complemented by a photoionization detector. This clinical prospective study involved 127 individuals, divided into two groups 46 with lung cancer stage I-II-III confirmed by computerized tomography or positron emission tomography-imaging techniques and histology (biopsy), and 81 healthy controls. Both instruments provided a multivariate signal which, after being analysed by a machine learning algorithm, identified eight VOCs that could distinguish lung cancer patients from healthy ones. The eight VOCs are 2-pentanone, 2-hexenal, 2-hexen-1-ol, hept-4-en-2-ol, 2-heptanone, 3-octen-2-one, 4-methylpentanol, 4-methyl-octane. Results show that GC-IMS identifies lung cancer with respect to the control group with a diagnostic accuracy of 88%. Sensitivity resulted as being 85%, and specificity was 90%-Area Under the Receiver Operating Characteristics 0.91. The contribution made by the e-nose was also important, even though the results were slightly less sensitive with an accuracy of 71.6%. Moreover, of the eight VOCs identified as potential biomarkers, five VOCs had a high sensitivity (p⩽ 0.06) for early stage (stage I) lung cancer.