Work

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

Year: 2026

Type: article

Abstract: • Integrated analysis identifies RPL8 as a highly specific diagnostic (AUC=0.95) and prognostic biomarker in HCC. • RPL8 promotes tumor proliferation, migration, and glutathione metabolism via the MYC/CDK1/CCNB1 signaling axis. • High RPL8 expression in malignant cells is spatially associated with immune-excluded niches, indicating suppressed anti-tumor immunity. • RPL8 depletion sensitizes HCC cells to the mTOR inhibitor sirolimus, revealing a targetable pathway dependency. Ribosomal protein L8 (RPL8) is up-regulated in hepatocellular carcinoma (HCC), yet its clinical value and microenvironment role remain unclear. Multi-omics (TCGA, CPTAC), scRNA-seq (GSE146115) and spatial transcriptomics were integrated; function was tested by RPL8 knockdown, proliferation/migration assays and drug-sensitivity screens. RPL8 mRNA/protein were markedly elevated ( p < 0.001) with AUC 0.95 for diagnosis. High RPL8 independently predicted shorter overall (HR 1.42) and disease-specific survival (HR 1.35). Mechanistically, RPL8 co-activated MYC/G2M signaling, rewired glutathione metabolism and correlated with cell-cycle/DNA-repair scores ( p < 0.001). scRNA-seq showed selective RPL8 enrichment in malignant hepatocytes and exhausted CD8 + T cells; spatial maps revealed tumor-confined expression inversely linked to immune infiltration ( p < 0.01). Silencing RPL8 suppressed proliferation, migration and glutathione synthesis ( p < 0.001), while sensitizing cells to sirolimus and sclareol ( p < 0.05). RPL8 drives HCC progression and immune evasion, qualifying it as a diagnostic biomarker and therapeutic target.

Source: Translational Oncology

DOI: 10.1016/j.tranon.2025.102663