Single-cell and bulk transcriptomic analyses reveal prognostic polyamine metabolism heterogeneity and plasma B cell interactions in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) exhibits significant metabolic heterogeneity, but the relationships among polyamine metabolism, tumor progression, and the immune microenvironment remain unclear. This study integrated multiple single-cell and bulk transcriptome datasets from HCC to systematically characterize polyamine metabolism features and their clinical significance. Our results showed that malignant hepatocytes with high polyamine metabolic activity displayed higher levels of copy number variation and were enriched in malignancy-related programs, including cell proliferation, G2/M checkpoint, and DNA repair; this feature was associated with poor patient prognosis. A nine-gene prognostic model based on polyamine metabolism-related genes demonstrated stable risk stratification ability in the TCGA-LIHC, ICGC-LIRI, and GSE144269 cohorts. Immune microenvironment analysis indicated that polyamine metabolism scores were correlated with immune cell infiltration and immune regulatory molecule expression, particularly with plasma cell/B-cell infiltration. Further re-clustering identified multiple plasma cell/B-cell subsets, among which proliferative B cells were enriched in tumor tissues and correlated with worse prognosis. Cell-cell communication analysis revealed stronger interactions between malignant hepatocytes with high polyamine metabolic activity and plasma cell subsets. In vitro experiments showed that knockdown of PSMA7 or PSMB2 in MCC97H and Bel7402 cells significantly inhibited cell viability, clone formation, and migration. In conclusion, polyamine metabolism may participate in HCC progression by shaping malignant hepatocyte states and the plasma cell/B-cell immune ecosystem. PSMA7 and PSMB2 are polyamine metabolism-related prognostic genes and candidate functional biomarkers; however, their direct involvement in polyamine metabolism and their value as therapeutic targets require further validation.