Integrating Single-Cell, Bulk, and Spatial Transcriptomics Unveils a Novel Ribosome Biogenesis-Related Prognostic Model and Defines RPS19BP1 as a Pro-Oncogenic Regulator in Lung Adenocarcinoma

Dysregulation of ribosome biogenesis is increasingly recognized as a hallmark of tumor malignancy, yet its prognostic implications in lung adenocarcinoma (LUAD) remain incompletely characterized. This study aimed to construct a ribosome biogenesis-related prognostic model for LUAD and explore its potential relevance to the tumor immune microenvironment. Single-cell and bulk RNA sequencing data were integrated to identify ribosome biogenesis-related genes (RBRGs), from which a prognostic risk score was established via Cox regression, LASSO regression, and multivariate Cox analyses and validated in two independent GEO cohorts. Associations between the risk score and tumor mutation burden, immune infiltration, and computationally inferred immunotherapy response were systematically evaluated. In vitro experiments were performed to characterize the biological function of RPS19BP1, a key gene in the model. A total of 262 RBRGs were identified, and the derived 14-gene risk score demonstrated prognostic value across three cohorts (TCGA: 1-, 2-, 3-year AUC = 73.08, 72.44, 72.20; GSE68571: 1-, 2-, 3-year AUC = 67.93, 73.24, 77.59; GSE8894: 1-, 2-, 3-year AUC = 75.56, 72.99, 71.77). The low-risk group exhibited a more immunocompetent tumor microenvironment, whereas the high-risk group was associated with an immunosuppressive phenotype. Knockdown of RPS19BP1 significantly attenuated the proliferation, migration, and invasion of LUAD cells. This multi-omics-derived prognostic model showed prognostic potential in retrospective LUAD cohorts, is associated with distinct immune infiltration patterns, and identifies RPS19BP1 as a pro-oncogenic regulator in LUAD.