Association between Ribosomal Protein Gene Dysregulation and Tumor Biodiversity of Hepatocellular Carcinoma

Background: Tumor cells are characterized by a higher production of ribosomes, which are necessary for maintaining enhanced cell growth and subsequent cell division. An increase in ribosome production is associated with aberrant ribosome biogenesis homeostasis, representing specific hallmarks of cancer cells. However, its association with the hepatocellular carcinoma (HCC) microenvironment remains poorly understood. Methods: Using single-sample gene set enrichment analysis (ssGSEA), an RPLscore was constructed to estimate the dysregulation of ribosomal protein large (RPL) genes. The expression of RPL genes and their association with clinical outcomes and the tumor microenvironment (TME) were systematically investigated using bulk-seq and single-cell RNA-seq (scRNA-seq). Results: High expression levels of RPL in HCC were associated with poorer overall survival (OS) (P < 0.001). The RPL score evaluated the RPL gene and verified its independent prognostic value for both OS and relapse-free survival (P = 0.0074 and P < 0.001, respectively). TME analysis indicated that RPL gene dysregulation was closely associated with T cell exhaustion, myeloid-derived suppressor cell (MDSC) infiltration, and vascular dysplasia may be promoted by arginine deficiency (P = 7.6 × 10-10). The scRNA-seq data suggested that the RPL score was positively and significantly associated with the tumor biodiversity score (ITH score). Conclusion: The study highlights the prognostic value of the RPL score and its potential role in mediating immune evasion of HCC, which may provide an impetus for the development of new targets for the treatment of HCC.