Development and internal validation of nomograms based on plasma metabolites to predict non‐small cell lung cancer risk in smoking and nonsmoking populations

BACKGROUND: Lung cancer has significantly higher incidence and mortality rates worldwide. In this study, we analyzed the metabolic profiles of non‐small cell lung cancer (NSCLC) patients and constructed prediction models for smokers and nonsmokers with internal validation. METHODS: Plasma was collected from all patients enrolled for metabolic profiling by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The total population was divided into two groups according to smoking or not. Statistical analysis of metabolites was performed separately for each group and prediction models were constructed. RESULTS: A total of 1723 patients (1109 NSCLC patients and 614 healthy controls) were enrolled from the affiliated hospital during 2018 to 2021. After grouping by smoking history, each group was statistically analyzed and prediction models were constructed, which resulted in eight indicators (propionylcarnitine, arginine, citrulline, etc.) significantly associated with lung cancer risk for smokers and eight indicators (dodecanoylcarnitine, hydroxybutyrylcarnitine, asparagine, etc.) for nonsmokers (p < 0.05). The smoker model indicated an AUC of 0.860 in the training set and 0.850 in the validation set. The nonsmoker model showed an AUC of 0.783 in the training set and 0.762 in the validation set. Further calibration tests for both models indicated excellent goodness‐of‐fit results. CONCLUSIONS: In this study, we found a series of metabolites significantly associated with lung cancer incidence and constructed respectively prediction models for NSCLC risk in smokers and nonsmokers, with internal validation to confirm the efficiency to discriminate lung cancer risk in both smoking and nonsmoking states.