Abstract Early cancer detection greatly increases the chances for successful treatment, but available diagnostics for some tumours, including lung adenocarcinoma (LA), are limited. An ideal early-stage diagnosis of LA for large-scale clinical use must address quick detection, low invasiveness, and high performance. Here, we conduct machine learning of serum metabolic patterns to detect early-stage LA. We extract direct metabolic patterns by the optimized ferric particle-assisted laser desorption/ionization mass spectrometry within 1 s using only 50 nL of serum. We define a metabolic range of 100–400 Da with 143 m/z features. We diagnose early-stage LA with sensitivity~70–90% and specificity~90–93% through the sparse regression machine learning of patterns. We identify a biomarker panel of seven metabolites and relevant pathways to distinguish early-stage LA from controls ( p &lt; 0.05). Our approach advances the design of metabolic analysis for early cancer detection and holds promise as an efficient test for low-cost rollout to clinics.

Machine learning of serum metabolic patterns encodes early-stage lung adenocarcinoma