Abstract
BackgroundThe mixture of volatile organic compounds in the headspace gas of urine may be able to distinguish lung cancer patients from relevant control populations.MethodsSubjects with biopsy confirmed untreated lung cancer, and others at risk for developing lung cancer, provided a urine sample. A colorimetric sensor array was exposed to the headspace gas of neat and pre-treated urine samples. Random forest models were trained from the sensor output of 70 % of the study subjects and were tested against the remaining 30 %. Models were developed to separate cancer and cancer subgroups from control, and to characterize the cancer. An additional model was developed on the largest clinical subgroup.Results90 subjects with lung cancer and 55 control subjects participated. The accuracies, reported as C-statistics, for models of cancer or cancer subgroups vs. control ranged from 0.795 – 0.917. A model of lung cancer vs. control built using only subjects from the largest available clinical subgroup (30 subjects) had a C-statistic of 0.970. Models developed and tested to characterize cancer histology, and to compare early to late stage cancer, had C-statistics of 0.849 and 0.922 respectively.ConclusionsThe colorimetric sensor array signature of volatile organic compounds in the urine headspace may be capable of distinguishing lung cancer patients from clinically relevant controls. The incorporation of clinical phenotypes into the development of this biomarker may optimize its accuracy.
Highlights
The mixture of volatile organic compounds in the headspace gas of urine may be able to distinguish lung cancer patients from relevant control populations
In the current discovery level study we report on the accuracy of colorimetric sensor array (CSA) derived signatures of the headspace gas of urine to detect and characterize lung cancer
Study subjects were included as controls if they were at risk for developing lung cancer based on age > 40 years and tobacco use of at least 10 pack-years, and/or a family history of lung cancer, and/or the presence of chronic obstructive pulmonary disease (COPD); or if they presented with an indeterminate lung nodule 8–30 mm in diameter that was confirmed to be benign based on biopsy or serial imaging
Summary
The mixture of volatile organic compounds in the headspace gas of urine may be able to distinguish lung cancer patients from relevant control populations. Urine is a non-invasively collected biospecimen that has been relatively under-represented as a source of potential molecular biomarkers of lung cancer. Volatile organic compounds (VOCs) are present in very low concentrations in the headspace gas of urine samples. There is a greater diversity of VOC classes in the urine than other biospecimen sources where VOCs can be measured, such as breath, skin, blood, and buccal mucosa [9].
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