肝細胞癌におけるRPL8の予後予測バイオマーカーおよび治療標的としての統合空間および単一細胞トランスクリプトミクス解析

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.