Development of a Non-invasive Diagnostic Method for Esophageal Squamous Cell Carcinoma by Gas Chromatographic Analysis of Exhaled Breath.

Objectives: Since esophageal carcinoma progresses asymptomatically, for many patients the disease is already advanced at the time of diagnosis. The main methods that are currently used to diagnose esophageal carcinoma are upper gastrointestinal radiographic contrast examinations and upper gastrointestinal endoscopy, but early discovery of this disease remains difficult. There is a need to develop a diagnostic method using biomarkers that is non-invasive while both highly sensitive and specific. Materials and Methods: Exhaled breath was collected from 17 patients with esophageal squamous cell carcinoma (ESCC), as well as 9 control subjects without history of any cancer. For each fasting subject, 1L of exhaled breath was collected in a gas sampling bag. Volatile organic compounds (VOCs) were then extracted from each sample using Solid phase micro-extraction (SPME) fibers and analyzed by gas chromatography-mass spectrometry (GC-MS). Results: Levels of acetonitrile, acetic acid, acetone, and 2-butanone in exhaled breath were significantly higher in the patient group than in the control group (p = 0.0037, 0.0024, 0.0024 and 0.0037, respectively). ROC curves were drawn for these 4 VOCs, and the results for the area-under-the-curve (AUC) indicated that ESCC patients can be identified with a high probability of 0.93. Conclusion: We found distinctive VOCs in exhaled breath of ESCC patients. These VOCs have a potential as new clinical biomarkers for ESCC. The measurement of VOCs in exhaled breath may be a useful, non-invasive method for diagnosis of ESCC.