Integrated analysis of single-cell and bulk-RNA sequencing data reveals drug therapeutic targets and prognostic biomarkers related to ribosome biogenesis in hepatocellular carcinoma

Background: Ribosome biogenesis is involved in the progression of hepatocellular carcinoma (HCC), but the specific mechanisms and diagnostic values of ribosome biogenesis-related genes (RBRGs) in HCC remain unclear. Objectives: We aimed to explore potential therapeutic targets in HCC from RBRGs. Methods: The differentially expressed RBRGs (DE-RBRGs) were explored using publicly available bulk RNA-sequencing data. Cox regression analysis was employed to evaluate the prognostic significance of the DE?RBRGs. The optimal machine learning algorithm was selected to construct a prognostic model. The predictive performance of the model was assessed using Kaplan?Meier analysis and receiver operating characteristic (ROC) curves. Single?cell RNA?sequencing data were subsequently utilized to identify key cell populations and the corresponding DE?RBRGs. Results: Bioinformatics analyses revealed 88 DE-RBRGs, predominantly enriched in ribosome biogenesis-related functions and pathways. The univariate Cox regression identified 12 DE-RBRGs with prognostic values. Following, the optimal machine learning algorithm (StepCox [forward] + SuperPC) was selected to construct a prognostic model. Survival analysis demonstrated that patients in the low-risk group exhibited markedly prolonged lifespan relative to their high-risk counterparts. ROC curves confirmed the predictive accuracy of this prognostic model in both training and validation cohorts. These 12 DE-RBRGs were significantly associated with immune cell infiltration, tumor immune evasion and drug sensitivity. Analysis of single-cell sequencing data identified hepatocytes as central mediators of HCC pathogenesis, which was associated with high expression of two DE-RBRGs: Nucleophosmin 1 (NPM1) and Ras-Related Nuclear Protein (RAN). Conclusion: NPM1 and RAN, which are highly expressed in hepatocytes, may serve as potential therapeutic targets in HCC. Their established roles in ribosome biogenesis could drive the development of novel therapies targeting this pathway.