Abstract
OBJECTIVES: The prognosis for advanced-stage non-small cell lung cancer (NSCLC) is usually poor. However, survival may be variable and difficult to predict. In the current study, we aimed to identify circulating metabolites as potential predictive biomarkers for overall survival of advanced-stage (III/IV) NSCLC patients treated with first-line platinum-based chemotherapy. MATERIALS AND METHODS: Using two-stage study design, we performed global metabolomic profiling in blood of 220 advanced-stage NSCLC patients, including 110 with poor survival and 110 with good survival. Metabolomic profiling was conducted using Metabolon platform. The association of each metabolite with survival was assessed by Cox proportional hazard regression model with adjustment for covariates. RESULTS AND CONCLUSION: We found levels of 4 metabolites, caffeine, paraxanthine, stachydrine, and methyl glucopyranoside (alpha+beta), differed significantly between NSCLC patients with poor and good survival in both discovery and validation phases (P<0.05). Interestingly, majority of the identified metabolites are involved in caffeine metabolism, and 2 metabolites are related to coffee intake. In fact, caffeine metabolism pathway was the only significant pathway identified which significantly differed between NSCLC patients with poor and good survival (P=1.48E-07) in the pathway analysis. We also found 4 metabolites whose levels were significantly associated with good survival in both discovery and validation phases. Strong cumulative effects on overall survival were observed for these 4 metabolites. In conclusion, we identified a panel of metabolites including metabolites in caffeine metabolism pathway that may predict survival outcome in advanced-stage NSCLC patients. The identified small metabolites may be useful biomarker candidates to help identify patients who may benefit from platinum-based chemotherapy.