The prognostic impact of tryptophan on non-small cell lung cancer survival: insights from plasma essential amino acids

Essential amino acids (EAAs) play a critical role in the metabolism of both tumor and immune cells, thereby potentially affecting tumor prognosis via multiple mechanisms. However, few studies have explored the impact of individual or total EAA levels on the survival outcomes of patients with non-small cell lung cancer (NSCLC). Metabolomics technology was employed to measure plasma levels of eight EAAs and kynurenine (Kyn) in NSCLC patients. Cox proportional hazards regression model was applied to assess the association between individual EAA levels and the risk of NSCLC related mortality. The combined effect of EAAs on mortality risk in NSCLC patients was further evaluated using multiple statistical models including weighted quantile sum (WQS) regression, quantile-based g computation (qgcomp), and Bayesian kernel machine regression (BKMR) models. Finally, a Random Forest (RF) model was developed to evaluate the prognostic value of the Trp/Kyn ratio in predicting the mortality risk in NSCLC patients. A total of 422 NSCLC patients were included in the analyses. During the median follow-up period of 40.71 months, 300 deaths were recorded. Multivariable Cox regression analyses revealed that six EAAs were significantly associated with a reduced mortality risk, among which Trp exhibited the strongest inverse association (HR: 0.44, 95%CI: 0.31–0.62). More importantly, a significant inverse association between EAA levels and mortality risk was consistently identified across all three models, particularly in patients with advanced-stage NSCLC. Trp was confirmed as the primary contributor to this combined effect, especially in the advanced NSCLC subgroup. Furthermore, a higher Trp/Kyn ratio was associated with a reduced mortality risk in NSCLC patients. Integrating the Trp/Kyn ratio with key clinical factors (smoking status, cancer stage, and surgery) into a Random Forest model significantly enhanced the prediction of 5-year mortality (test set AUC: 0.759). The plasma EAAs were inversely associated with the risk of death in NSCLC patients, especially in those with advanced-stage disease. Among the eight EAAs, Trp emerged as the primary contributor. The Trp/Kyn ratio served as a valuable biomarker for risk stratification.