A nanomaterial-based breath test for distinguishing gastric cancer from benign gastric conditions

• Published in: British journal of cancer 2013-03, Vol.108 (4), p.941-950
• Main Authors: Xu, Z-q, Broza, Y Y, Ionsecu, R, Tisch, U, Ding, L, Liu, H, Song, Q, Pan, Y-y, Xiong, F-x, Gu, K-s, Sun, G-p, Chen, Z-d, Leja, M, Haick, H
• Format: Article
• Language: English
• Subjects: 631/61/350/59; 692/699/1503; 692/699/67/1504/1829; 692/700/139; Alcohol; Analytical chemistry; Biological and medical sciences; Biomarkers - analysis; Biomedical and Life Sciences; Biomedicine; Biopsy; Breath tests; Breath Tests - methods; Cancer; Cancer Research; Chromatography; Classification; Confounding (Statistics); Developed countries; Disease; Drug Resistance; Endoscopy; Epidemiology; Female; Gastric cancer; Gastroenterology. Liver. Pancreas. Abdomen; Helicobacter pylori; Humans; Male; Mass spectrometry; Medical research; Medical sciences; Middle Aged; Molecular Diagnostic Techniques; Molecular Diagnostics; Molecular Medicine; Nanomaterials; Nanostructures; Oncology; Pattern recognition; Pilot Projects; Prediction models; Scientific imaging; Sensitivity; Sensors; Stomach Neoplasms - diagnosis; Stomach Ulcer - diagnosis; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tobacco; Tumors; Ulcers; VOCs; Volatile organic compounds; Volatile Organic Compounds - analysis
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2013.44

Background: Upper digestive endoscopy with biopsy and histopathological evaluation of the biopsy material is the standard method for diagnosing gastric cancer (GC). However, this procedure may not be widely available for screening in the developing world, whereas in developed countries endoscopy is frequently used without major clinical gain. There is a high demand for a simple and non-invasive test for selecting the individuals at increased risk that should undergo the endoscopic examination. Here, we studied the feasibility of a nanomaterial-based breath test for identifying GC among patients with gastric complaints. Methods: Alveolar exhaled breath samples from 130 patients with gastric complaints (37 GC/32 ulcers / 61 less severe conditions) that underwent endoscopy/biopsy were analyzed using nanomaterial-based sensors. Predictive models were built employing discriminant factor analysis (DFA) pattern recognition, and their stability against possible confounding factors (alcohol/tobacco consumption; Helicobacter pylori ) was tested. Classification success was determined (i) using leave-one-out cross-validation and (ii) by randomly blinding 25% of the samples as a validation set. Complementary chemical analysis of the breath samples was performed using gas chromatography coupled with mass spectrometry. Results: Three DFA models were developed that achieved excellent discrimination between the subpopulations: (i) GC vs benign gastric conditions, among all the patients (89% sensitivity; 90% specificity); (ii) early stage GC (I and II) vs late stage (III and IV), among GC patients (89% sensitivity; 94% specificity); and (iii) ulcer vs less severe, among benign conditions (84% sensitivity; 87% specificity). The models were insensitive against the tested confounding factors. Chemical analysis found that five volatile organic compounds (2-propenenitrile, 2-butoxy-ethanol, furfural, 6-methyl-5-hepten-2-one and isoprene) were significantly elevated in patients with GC and/or peptic ulcer, as compared with less severe gastric conditions. The concentrations both in the room air and in the breath samples were in the single p.p.b. v range, except in the case of isoprene. Conclusion: The preliminary results of this pilot study could open a new and promising avenue to diagnose GC and distinguish it from other gastric diseases. It should be noted that the applied methods are complementary and the potential marker compounds identified by gas-chromatography/mass spectrom