Open Access Peer-reviewed Research Article

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

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Submitted   Nov 15, 2024
Published   Apr 15, 2025
Issue    Vol 7 (2025)
DOI   10.25082/CCR.2025.01.001

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Zhimin Lu
Department of Outpatient, Affiliated Hospital of Jiaxing University, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China
Sicong Xu
Geneplus-Beijing Institute, Peking University Medical Industrial, Beijing, China
Guofeng Zhao
Beijing Moyin Biotechnology, Beijing, China
Ziyi Niu
The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
Guoxin Hou corresponding author
Department of Oncology, Affiliated Hospital of Jiaxing University, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China

Abstract

Background: Tumor cells are characterized by a higher production of ribosomes, which are necessary for maintaining enhanced cell growth and subsequent cell division.
Aim: The study aimed to develop a prognostic ‌RPL score‌ for hepatocellular carcinoma (HCC) and explore its association with immune evasion mechanisms mediated by tumor microenvironment alterations.
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.

Keywords
Hepatocellular carcinoma, Ribosome protein large (RPL) genes, tumor microenvironment (TME)

Article Details

Supporting Agencies
This research was supported by the Key Discipline Established by Zhejiang Province and Jiaxing City Joint-Oncology Medicine (2023-SSGJ-001), National Clinical Key Specialty Construction Project-Oncology department (2023-GJZK-001), Jiaxing Key Laboratory of Clinical Laboratory Diagnosis and Transformation Research (2023-lcjyzdyzh), 2023 Jiaxing Key Discipline of Nursing (Supporting Subject) (2023-ZC-007), Science Technology Project of Jiaxing-Key Research Project (2024BZ20004), and Jiaxing Key Laboratory of Oncology Radiotherapy (2021-zlzdsys). All study sponsors had no role in the study design, collection, analysis, and interpretation of data.
How to Cite
Lu, Z., Xu, S., Zhao, G., Niu, Z., & Hou, G. (2025). Association between Ribosomal Protein Gene Dysregulation and Tumor Biodiversity of Hepatocellular Carcinoma. Current Cancer Reports, 7, 254-268. https://doi.org/10.25082/CCR.2025.01.001
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

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