Integrated spatial and single-cell transcriptomics reveals RPL8 as a prognostic biomarker and therapeutic target in...

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Ribosomal protein L8 (RPL8) is upregulated in hepatocellular carcinoma (HCC).
• The clinical significance and microenvironment role of RPL8 in HCC are not well understood.

Purpose of the Study:

• To investigate the clinical value and microenvironment role of RPL8 in HCC.
• To explore RPL8 as a potential diagnostic biomarker and therapeutic target for HCC.

Main Methods:

• Integrated multi-omics data (TCGA, CPTAC) and single-cell/spatial transcriptomics (GSE146115).
• Performed RPL8 knockdown, proliferation/migration assays, and drug-sensitivity screens.
• Analyzed RPL8 expression, survival prediction, signaling pathways, and immune cell infiltration.

Main Results:

• RPL8 mRNA/protein levels were significantly elevated in HCC, showing high diagnostic accuracy (AUC 0.95).
• High RPL8 independently predicted shorter overall and disease-specific survival.
• RPL8 promoted HCC progression by activating MYC/G2M signaling, altering glutathione metabolism, and contributing to immune evasion.
• RPL8 silencing reduced proliferation, migration, glutathione synthesis, and sensitized HCC cells to specific drugs.

Conclusions:

• RPL8 plays a crucial role in driving HCC progression and immune evasion.
• RPL8 serves as a valuable diagnostic biomarker for HCC.
• RPL8 represents a potential therapeutic target for HCC treatment.