OMIC era in the diagnosis of the diseases: volatilome and volatolome
To find alternative tools in cancer diagnosis in an earlier and more precise manner, researchers have explored the use of Metabolomics, specifically the volatile organic compounds (VOC) to detect these complex diseases.
VOC are carbon-based chemicals, volatile at room temperature and pressure, and source of most odors. Being produced during metabolic processes in millions of cells simultaneously, thus they are potentially releasing in an extracellular way on a detectable scale and may be emitted from different areas of the body prone to odor production e.g., scalp, axillae, feet, groin, oral cavity. These also can be excreted through different biofluids as saliva, breath, blood, sputum, feces, sweat, urine and may serve as ideal clinical biomarkers for several pathophysiological processes. The entire set of VOC produced by an organism is called Volatilome, and their accumulation inside and outside of the body reflects a unique metabolic state in an organism [6, 22, 23]. This knowledge is too old; the ancient Greek and Chinese human noses were the first to identify and describe the diagnostic potential of VOC in the diseases through the smell of different biological samples such as urine and sputum. Based on this ancestral knowledge, we know the VOC potential in the medical field, and ever since, our sense of smell has been used in medical practice as a more precise and less invasive diagnostic tool for the detection of several diseases [24]. Among the several diseases characterized by a specific odor are diabetes (rotten apple odor in the breath), scurvy (putrid body odor), cholera (rice water), trimethylaminuria (rotten fish-like odor in the breath, vaginal fluid, sweat and urine), phenylketonuria (musty odor), cystic fibrosis (chloride), or typhoid fever (baked bread body odor), etc. [25, 26].
Interestingly, in the last few decades, the diagnosis potential of VOC has focused on the search of the volatile profiles of many cancers in all the biofluids as the urine, feces, exhaled breath, and saliva of patients.
The rationale for this is that cancer cells have different metabolic or biochemical requirements in comparison from normal cells, due to the genetic alterations that acquire and that allow them to proliferate outside the context of normal tissue development [27]. Therefore, the metabolic and bioenergetic alterations presented by tumor cells lead to a VOC profile different from that of healthy cells. These VOC profiles are useful for the diagnostic of cancer, predict patient response towards chemotherapies or treatment and monitor disease recurrences [28].For example, the lack of sensitive and specific biomarkers for the early detection of prostate cancer led a Portuguese research group to investigate the performance of VOC present in the urine of patients as potential markers for this cancer in a metabolomic approach based on the analytical tool, the Gas Chromatography-Mass Spectrometry (GC-MS), finding a urinary profile of VOC different from that of cancer-free subjects with 78% sensitivity, 94% specificity and 86% accuracy [29].
A research group in the UK assessed the utility of VOC as feces biomarkers for colorectal neoplasia by headspace extraction followed by GC-MS. This group found that Propan-2-ol was the volatile organic compound most strongly associated with cancer, and 3-methylbutanoic acid or DL-menthol was the only volatile organic compound negatively associated with cancer. These VOC showed a diagnostic ability of sensitivity 87.9% and specificity 84.6% in the identification of colorectal adenocarcinoma [30].
Another example was research in which the gastric cancer was correlated with specific VOC biomarkers in the exhaled breath of a South American population. The exhaled VOC were analyzed by GC-MS and by a chemical gas sensor based on gold nanoparticles functionalized with octadecylamine ligands. Six VOC showed statistically significant differences between the cancer patients and the controls group (e.g., hexadecane and octadecane in the gastric cancer group, while eicosane and 1-cyclohexyl-2-(cyclohexylmethyl) pentane were identified as biomarkers in the control group).
The sensor data responses to the breath samples yielded 97% accuracy, 100% sensitivity and 93% specificity [31].Recently in Japan, the salivary metabolomic profile of oral squamous cell carcinoma was established through VOC analysis as potential biomarkers for the diagnosis of oral cancer through a method combining thin-film microextraction based on a ZSM 5/polydimethylsiloxane hybrid film coupled with GC-MS in saliva samples of oral cancer patients and healthy controls in which eighty kinds of volatile metabolites that were detected and identified and were classified as alcohols, ketones, hydrocarbons, aldehydes, organic acids, esters, phenols, etc. Among them, twelve COV were selected as potential oral cancer biomarkers for their use as non- invasive tools for the possible diagnosis of this cancer [32].
The above were just some examples of the vast literature that currently exists on the analysis of VOC for the diagnosis of different cancers through non-invasive samples and analytical methods.
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