A high-performance metabolomic diagnostic panel for early-stage non-small cell lung cancer detection based on UPLC‒MS/MS

Abstract Lung cancer is the most common cancer in the world and has a consistently high mortality rate, with the majority of patients being diagnosed at an advanced stage. This study aimed to identify potential biomarkers through metabolomics to provide clues for the diagnosis and treatment of early-stage non-small cell lung cancer (NSCLC). We enrolled two prospective cohorts with a total of 180 patients (115 patients with I-II a NSCLC and 65 healthy controls) and tested serum samples for tumour markers, cytokines, and 306 metabolites by ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry (UPLC‒MS/MS). In both the discovery and validation cohorts, there were 57 differentially abundant metabolites in the serum between patients with early-stage NSCLC and healthy controls, which were concentrated in the fatty acid metabolic pathway and amino acid metabolic pathway. Finally, three metabolites with significant differences were screened as isoleucine, 5Z-dodecenoic acid and 9E-tetradecenoic acid. The AUC of centralized combined diagnosis reached 0.95. This study provides new evidence that abnormalities in valine, leucine, and isoleucine metabolism and dysregulation of fatty acid synthesis may play important roles in the development of NSCLC.