Noninvasive Breathomics for Developing Carbonyl Biomarkers in Esophageal Cancer

Background Despite being the gold standard for esophageal cancer (EC) diagnosis, the invasiveness and cost limit the use of upper gastrointestinal endoscopy for primary screening. We evaluated the potential of aldehyde profiling in exhaled breath condensate (EBC), a noninvasively obtained biofluid, as an EC diagnostic biomarker. Methods EBC, plasma, or saliva samples were collected from 152 patients with EC and 63 healthy controls (HC); aldehyde concentrations in EBC and plasma were measured using liquid chromatography–tandem mass spectrometry. Saliva microbiota was analyzed by 16S rRNA sequencing, focusing on oral acetaldehyde-producing bacteria. Results Among eight different aldehydes measured using EBC samples, acetaldehyde and formaldehyde concentrations were significantly higher in patients with EC than in HC, with elevations observed in both early and advanced-stage disease. Plasma acetaldehyde and formaldehyde levels were also increased in patients with EC compared with that in HC. EBC acetaldehyde and formaldehyde were identified as diagnostic biomarkers (areas under the curve: 0.77/0.87, sensitivities: 78%/89%, specificities: 70%/79%). It remains unclear whether the salivary microbiota influence the acetaldehyde concentration in EBC. Conclusions Acetaldehyde and formaldehyde in EBC are potential diagnostic biomarkers for EC. EBC is a noninvasive sample useful for screening with potential utility for early detection of EC.