Investigation of sweat VOC profiles in assessment of cancer biomarkers using HS-GC-MS

Abstract

Volatile organic compounds (VOCs) have been studied in biological samples in order to be related to the presence of diseases. Sweat can represent substances existing in blood, has less complex composition (compared with other biological matrices) and can be obtained in a non-invasive way. In this work, sweat patches were collected from healthy controls and volunteers with cancer. Static Headspace was used for VOCs extraction, analysis was performed by gas chromatography coupled with mass spectrometry. Principal Components Analysis was used to investigate data distribution. Random Forest was employed to develop classificatory models. Controls and positive cases could be distinguished with maximum sensitivity and specificity (100% of accuracy) in a model based on the incidence of 2-ethyl-1-hexanol, hexanal and octanal. Discrimination between controls, primary tumors and metastasis was achieved using a panel with 11 VOCs. Balanced accuracy of more than 70% was obtained for the classification of a neoplasm site. Total n-aldehydes presented to be strongly correlated with staging of adenocarcinomas, while phenol and 2,6-dimethyl-7-octen-2-ol were correlated with Gleason score. These findings corroborate with the development of accessible screening tools based on VOC analysis and highlight sweat as a promising matrix to be studied in a clinical context for cancer diagnosis.

The detection dogs test is more sensitive than real-time PCR in screening for SARS-CoV-2

“…Recently, a study identified a unique profile of VOCs in sweat samples for the diagnosis and staging of adenocarcinomas. In fact, it is suggested that sweat can represent substances in the blood, but owes an advantage of being less complex in chemistry than the blood 33 . The results in the present study also suggest the presence of a unique profile of VOCs in sweat samples of COVID-19 patients being detected by K9 dogs.…”

Beyond liquid biopsy: Toward non-invasive assays for distanced cancer diagnostics in pandemics

“…Recently, two review papers have addressed “skin metabolomic” ( Elpa et al, 2021 ) and “volatilome” ( Opitz and Herbarth, 2018 ), to encompass the possibilities of using sweat as a source of biomarkers for cancer diagnosis. Examples include Nonanedioic or azelaic acid for lung cancer ( Calderón-Santiago et al, 2015 ); n-aldehydes and 2-ethyl-1-hexanol ubiquitous in sweat of cancer patients and absent among healthy individuals ( Monedeiro et al, 2020b ). Table 4 provides examples of biomarkers within sweat and the associated cancer types.…”

“… Type of cancer Type of biomarker Method of detection/Targeted Biomarkers/Ref. Ovarian Amino acids Immunocapture/parallel reaction monitoring mass spectrometry - mat-KLK9 ( Filippou et al, 2017 ) Lung Metabolites Qualitative tandem liquid chromatography quadrupole time of flight mass spectrometry - Suberic acid, tetrahexose, trihexose, nonanedioic acid & monoglyceride ( Calderón-Santiago et al, 2015 ) Lung, Gastric, Prostate, Head, Kidney, pancreas Chiral alcohol Gas chromatography with mass spectrometry - 2-ethyl-1-hexanol, hexanal, octanal & 2,6 dimethyl-7-octen-2-ol ( Monedeiro et al, 2020a ) Head and Neck Metabolites Headspace solid-phase micro extraction (SPME) gas chromatography (GC) mass spectrometry (MS) – 81 VOMs as potential tumor markers ( Opitz and Herbarth, 2018 ) Prostate Amino acids Mass spectrometry – KLK4 ( Karakosta et al, 2016 ) Various Nucleic acids Real-time RT-PCR - DCD ( Sakurada et al, 2010 ) …”

Micro-Chamber/Thermal Extractor (µ-CTE) as a new sampling system for VOCs emitted by feces

“…Moreover, for breath analysis various sensors able to perform the analyses in real time, without any pre-concentration or storage, were created in the attempt to diagnose respiratory diseases 6 – 8 and even a standardized breath sampler was developed 1 . Except breath samples, other matrices, such as urine 9 – 11 , sweat 12 , human tissues 13 , saliva 14 , breast milk 15 , exudates 16 , or bacteria 17 – 21 were investigated in research articles and discussed in reviews 19 , 22 – 24 in order to discover valuable biomarkers of certain diseases. In case of feces samples, literature in the field is related mostly to identification of those VOCs markers of colorectal-cancer 25 – 28 , but nevertheless considerably less progress has been made with feces compared with investigating other biological matrices, especially breath and urine.…”