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

Abstract

Nowadays 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 (QMBs) complemented by a photoionization detector (PID). This clinical prospective study involved 127 individuals, divided into two groups: 46 with lung cancer stage I-II-III confirmed by computerized tomography (CT) or positron emission tomography—(PET) 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 (AUROC): 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.

GC-MS Techniques Investigating Potential Biomarkers of Dying in the Last Weeks with Lung Cancer

“…Five papers have reported urinary VOCs in lung cancer and named 51 identified VOCs as potential biomarkers of cancer [ 26 , 27 , 28 , 29 , 30 ] ( Table S12 ). It is interesting to note that the five VOCs we found increased towards death were also reported as potential biomarkers of lung cancer.…”

“…It is interesting to note that the five VOCs we found increased towards death were also reported as potential biomarkers of lung cancer. In the acid dataset, they were heptan-2-one [ 26 , 27 , 28 , 30 ], propan-2-one [ 28 ], cyclohexanone [ 29 ] and nonan-2-one [ 26 ]. In our alkali dataset, 2-ethylhexan-1-ol [ 26 , 27 ] increased towards death.…”

“…One paper, which aimed to use VOCs to diagnose lung cancer at an early stage, demonstrated that the eight VOCs they discovered had increasing abundance of these VOCs with each stage of the cancer [ 30 ]. Of these, heptan-2-one was present in our acid dataset.…”

Serum proteomics profiling identifies a preliminary signature for the diagnosis of early‐stage lung cancer

“…For instance, the analysis of volatile organic compounds from breath, by either an electronic nose device or gas chromatography‐mass spectrometry, has suggested the existence of a specific fingerprint or “breathprint” able to recognize lung cancer from both healthy donors and other pulmonary diseases [19, 20]. Cancer volatile organic compounds analysis has been also applied to urine samples, generating promising results [21]. In addition, urine proteomics combined with the development of a machine learning model generated a short list of differentially expressed proteins in lung cancer patients compared with healthy subjects [5].…”

C. elegans as a Powerful Tool for Cancer Screening

“…Therefore, a routine pancreatic cancer screening test, sensitive at an early stage, is needed. Differences exist among cancers in the human volatilome in the urine [ 45 , 67 , 68 , 69 ]. We hypothesized that knocking out in AWC olfactory neurons of C. elegans , a specific GPCR may lead to a chemotactic response specific to a single cancer type using a urine sample.…”