A high-resolution circulating metabolic atlas of lung adenocarcinoma progression supports early and accurate diagnosis.

Yang, Shouzhi; Qiao, Yongxia; Chen, Tianxiang; Yu, Wenjun; Zhao, Yuewei; Gu, Zhengying; Xie, Xin; Meng, Fanyu et al. · Cell Rep Med · 2026

prospective_cohort · Level II

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Abstract

Early diagnosis of lung adenocarcinoma (LUAD), particularly at the adenocarcinoma in situ (AIS) stage, is critical for curative intervention. Profiling blood-based metabolic progression offers a systemic view of tumorigenesis to enable robust, noninvasive early detection. To achieve this, we profile 2,836 serum samples from predominantly female, never-smoking Chinese cohorts spanning normal lung to invasive carcinoma using an ultrafast nanoparticle-enhanced mass spectrometry platform. This integrated retrospective and prospective cohort design enables the construction of a comprehensive metabolic atlas, revealing conserved metabolic perturbations that arise at the pre-invasive stage and progress with histologic severity. Guided by these trajectories, we develop a ten-metabolite diagnostic assay that demonstrates reproducible performance across independent cohorts (area under the curve 0.900 for overall; 0.860 for pre-invasive disease). Notably, assay efficacy remains consistent after adjusting for demographic and lifestyle confounders. These findings identify metabolic rewiring as an early hallmark of LUAD, with potential utility in population-level early detection.