Integrative Serum Metabolic Fingerprints Based Multi‐Modal Platforms for Lung Adenocarcinoma Early Detection and Pulmonary Nodule Classification

Identification of novel non-invasive biomarkers is critical for the early diagnosis of lung adenocarcinoma (LUAD), especially for the accurate classification of pulmonary nodule. Here, a multiplexed assay is developed on an optimized nanoparticle-based laser desorption/ionization mass spectrometry platform for the sensitive and selective detection of serum metabolic fingerprints (SMFs). Integrative SMFs based multi-modal platforms are constructed for the early detection of LUAD and the classification of pulmonary nodule. The dual modal model, metabolic fingerprints with protein tumor marker neural network (MP-NN), integrating SMFs with protein tumor marker carcinoembryonic antigen (CEA) via deep learning, shows superior performance compared with the single modal model Met-NN (p < 0.001). Based on MP-NN, the tri modal model MPI-RF integrating SMFs, tumor marker CEA, and image features via random forest demonstrates significantly higher performance than the clinical models (Mayo Clinic and Veterans Affairs) and the image artificial intelligence in pulmonary nodule classification (p < 0.001). The developed platforms would be promising tools for LUAD screening and pulmonary nodule management, paving the conceptual and practical foundation for the clinical application of omics tools.