A high-resolution circulating metabolic atlas of lung adenocarcinoma progression supports early and accurate diagnosis.
prospective_cohort · Level II
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- Record sourced from PubMed, PMID 42575093.
- Also identified by DOI 10.1016/j.xcrm.2026.102991.
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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.