Quantitative metabolomics identifies prognostic biomarkers associated with NSCLC after chemoradiotherapy

Abstract

Introduction: The high mortality of non-small cell lung cancer (NSCLC) is influenced by pre-treatment individual variability, yet reliable prognostic biomarkers are lacking, hindering precision therapy. Objectives: This study aimed to identify plasma metabolite biomarkers for predicting prognosis in stage III NSCLC patients using a targeted quantitative metabolomics approach. Methods: Plasma samples from 113 stage III NSCLC patients with long-term follow-up and 57 healthy controls were analyzed via LC-MS/MS-based targeted metabolomics. Patients were stratified into favorable and poor prognosis groups based on three-year survival. Differential metabolites were identified, and their association with overall survival was evaluated using Kaplan–Meier analysis. Results: Several metabolites differed between NSCLC patients and controls. Survival analysis revealed that elevated glutathione (GSH) levels were significantly associated with improved overall survival (p = 0.0013). Conversely, higher levels of glutamylglutamine (Glu-Gln) (p = 0.0117) and lysophosphatidylcholine 18:3 (LPC 18:3) (p = 0.0119) were correlated with poorer overall survival. Conclusion: This study identifies GSH and LPC 18:3 as promising prognostic biomarkers for stage III NSCLC. These findings provide new insights into patient stratification and the development of personalized treatment strategies.