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High performance exhaled breath biomarkers for diagnosis of lung cancer and potential biomarkers for classification of lung cancer

Exhaled breath analysis has emerged as a promising non-invasive method for diagnosing lung cancer (LC), whereas reliable biomarkers are lacking. Herein, a standardized and systematic study was presented for LC diagnosis, classification and metabolism exploration. To improve the reliability of biomarkers, a validation group was included, and quality control for breath sampling and analysis, comprehensive pollutants analysis, and strict biomarker screening were performed. The performance of exhaled breath biomarkers was shown to be excellent in diagnosing LC even in early stages (stage I and II) with surpassing 0.930 area under the receiver operating characteristic (ROC) curve (AUC), 90% of sensitivity and 88% of specificity both in the discovery and validation analyses. Meanwhile, in these two groups, diagnosing subtypes of LC attained AUCs over 0.930 and reached 1.00 in the two subtypes of adenocarcinomas. It is demonstrated that the metabolism changes in LC are possibly related to lipid oxidation, gut microbial, cytochrome P450 and glutathione S-transferase, and glutathione pathways change in LC progression. Overall, the reliable biomarkers contribute to the clinical application of breath analysis in screening LC patients as well as those in early stages.