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Tumor Discovery Volatile organic compounds for cancer screening

the identification and eradication of H. pylori as a key model that differentiates patients with gastric cancer from
preventative measure. Endoscopy made a significant controls. The AUC for their model was 0.92, with a sensitivity
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impact on gastric cancers not only by increasing the of 89.3% (95% confidence interval [CI]: 77.0 – 95.7) and
detection of early gastric cancers by enabling biopsies but specificity of 83.7% (95% CI: 74.5 – 90.9). Interestingly,
also by aiding in decreasing gastric cancer occurrence H. pylori status and proton-pump inhibitor independently
by allowing for the detection and implementation of predict exhaled ammonia concentrations, identifying a key
eradication therapy against H. pylori. The limitations of limitation of VOC screening as it remains susceptible to
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upper endoscopy are primarily related to its invasiveness interference from both endogenous and exogenous factors
and resultant potential patient discomfort, as well as the (Figure 1).
associated risks of the procedure, including bleeding or Similarly, a recent meta-analysis published in 2021
perforation. As with all technical procedures, the accuracy pooled the data from five studies exploring the role of
of endoscopy can vary based on the skill and experience of exhaled VOCs in the diagnosis of GI cancer. These studies
the endoscopist. Endoscopy remains the gold standard in analyzed endogenous VOCs in exhaled breath of patients
the detection of gastric cancer as it allows for the collection with biopsy-confirmed GI cancer. The pooled data analysis
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of biopsies for histological examination and definitive suggests that VOCs can be used to differentiate between
diagnosis. 69 gastric cancer and non-malignant gastric conditions with
Before 2010, the application of human breath analysis sensitivity of 85% and specificity of 89%, with diagnostic
was largely limited to urea breath testing for H. pylori odds ratio and AUC values reported as 41.30 and 0.93,
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infection, a hydrogen breath test for small bowel bacterial respectively. Durán-Acevedo et al. compared breath
overgrowth, and the concentration of exhaled nitric samples from 14 patients with gastric cancer and 15
oxide for the investigation of asthma. In 2013, exhaled controls. Using a novel solid-state sensor in addition to
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breath metabolites in 18 patients with biopsy-proven GC-MS, a significantly higher concentration of six VOCs
esophagogastric cancers were analyzed and compared to was identified in patients with gastric cancer, leading to
the concentrations of the metabolites in a control group a predictive model that identified patients with gastric
of 18 patients with biopsy-proven non-cancer diseases of cancer with a sensitivity of 100% and a specificity of 93%.
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the upper GI tract and 17 healthy controls. The study Similarly, Lee et al. determined that four VOCs (propanal,
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identified a significant increase in the concentration of acetamide, isoprene, and 1,3 propanediol) exhibit a gradual
hexanoic acid in the exhaled breath of the esophagogastric increase in concentration from normal control to early and
cancer patients compared to patients in the positive advanced gastric cancer (Figure 2). Analysis of the ROC
control and healthy control groups. In addition, there were curves for these four VOCs demonstrated that the AUC for
statistically significant increases in the concentrations gastric cancer prediction was highest (0.842) when three or
of phenols and their derivatives, methyl phenol and more VOCs were measured in tandem.
ethyl phenol, in the exhaled breath of patients with Intraluminal gas has also been used for VOC analysis
esophagogastric cancer, compared with the positive for gastric cancer diagnosis. Yang et al. reported on
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control, and healthy control groups. It was thought that using a combination of intraluminal and exhaled gas
these differences in concentrations were due to increased collecting during a prospective trial involving 259 patients
protein catabolism in gut microbiota and the upregulation undergoing endoscopy to discriminate between upper GI
of tyrosine metabolism in patients with esophagogastric cancer and healthy controls. Intraluminal VOC analysis
cancers. was better in discriminating upper GI cancer from
In 2015, Kumar et al. quantified exhaled breath benign controls when compared to exhaled VOC analysis
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VOCs from 210 patients with either esophagogastric (sensitivity: 91.23% vs. 81.75%, specificity: 90.65% vs.
adenocarcinoma, Barrett’s esophagus, benign upper 88.46%, and AUC: 0.930 vs. 0.877). Gastric cancer could
GI disease such as gastritis and gastric ulcer, or a also be detected with both intraluminal and exhaled breath
normal upper GI tract. The study identified 29 exhaled VOC analysis, which discriminated this patient population
molecules of interest, including 12 VOCs present at versus benign controls (sensitivity: 87.04% vs. 74%,
statistically significantly higher concentrations in patients specificity: 96.99% vs. 92.31%, and AUC: 0.983 vs. 0.889).
with esophagogastric cancers. The AUC using these At this time, more research is required to identify specific
12 molecules to discriminate patients with esophageal and and reliable VOC biomarkers associated with gastric cancer
gastric adenocarcinoma from those with non-malignant to improve its diagnostic accuracy. Although several models
conditions as well as healthy controls was 0.92 and 0.98, have been shown to differentiate between benign and
respectively. The authors further proposed a predictive malignant conditions, as well as discriminate between early

Volume 3 Issue 2 (2024) 8 doi: 10.36922/td.2061