A novel approach to non-invasive lung cancer screening via exhaled breath analysis using proton transfer reaction time-of-flight mass spectrometry.

Lung cancer (LC) remains a global public health problem. To minimize late diagnosis, new detection techniques are needed. The analysis of volatile organic compounds (VOCs) in human breath (the volatilome) represents a non-invasive alternative to current methods for the early detection of LC. In this study, VOCs were determined in the breath of individuals with LC (N= 22) and without LC (non-LC,N= 21) using proton transfer reaction time-of-flight mass spectrometry. Orthogonal partial least squares discriminant analysis and hierarchical cluster analysis were conducted on a subset of 54 VOC ions (out of 180). Twenty-one of the 54 VOC ions were detected in exhaled breath. CH4O3H+and C8H7NH+were found only in participants without cancer. Among the 19 common ions present in both cohorts, the intensities of 8 ions were statistically different. The LC/non-LC ratios were observed for C4H8O2H+, followed by C3H4OH+, C2H2OH+, C2H3ONH+, C3H4H+, C3H2H+, C4H8H+, and C6H8H+. Spearman correlation analysis could be used to differentiate metabolic processes or pathways between cohorts. Diagnostic ratio is a potential tool to classify individuals with or without LC. This study provides exploratory evidence for exhaled VOCs as potential LC biomarkers and positions them as a complement to current diagnostic pathways, with a potential role in supporting early triage and clinical decision-making.