Noninvasive assessment of core metastatic genes in lung adenocarcinoma: development of a predictive model integrating single-cell transcriptomics and radiomics

Background Lung adenocarcinoma (LUAD) leads to death primarily due to its high metastatic potential. Risk assessment methodologies currently predicated on histopathological and imaging features possess a limited capacity to predict metastatic potential. Therefore, integrating single-cell transcriptomics and CT radiomics to identify key molecular drivers of metastasis and establishing a noninvasive imaging prediction model for LUAD is important. Methods Bulk transcriptomic data and single-cell RNA sequencing (scRNA-seq) data were obtained from public database for analysis. Analytical tools (Seurat, inferCNV, Monocle, WGCNA, LASSO regression, GO/KEGG/GSEA, CellChat) were used for cellular profiling, trajectory analysis, gene identification, functional enrichment, and cell–cell communication. Immunohistochemistry (IHC) and RT-qPCR validated candidate genes at protein and mRNA levels. Additionally, a CT radiomics-based predictive model was developed for noninvasive gene expression assessment. Results ScRNA-seq analysis revealed a malignant cellular trajectory from primary to metastatic LUAD and identified a metastasis-associated subpopulation. Three consistently overexpressed genes (PSMB5, PSMB7 and SLC16A3) were correlated with poor prognosis. Functional studies indicated their synergistic roles in promoting tumor progression through cell cycle regulation, proteasome activity, and metabolic reprogramming. A CT radiomics model effectively predicted the combined expression of these genes (AUC = 0.765), linking imaging features to molecular phenotypes. Conclusion This study reveals that the synergistic expression pattern of PSMB5, PSMB7 and SLC16A3 is closely associated with lung adenocarcinoma metastasis and poor prognosis, confirming their potential value as prognostic biomarkers and therapeutic targets. The CT radiomics model offers a noninvasive tool for molecular phenotyping, aiding in preoperative precision assessment and advancing noninvasive clinical decision-making for LUAD.