Disorders of
polyamine metabolism may contribute to the development of
hepatocellular carcinoma (HCC), but the precise mechanism remains unknown. This study reports that
spermine synthase (SMS), an
enzyme involved in
polyamine biosynthesis, is overexpressed in HCC and not associated with hepatitis virus
infection in HCC patients. The results of analyzing the clinical data of HCC patients showed that SMS level as a categorical dependent variable was related to clinicopathological features of poor prognosis. Furthermore, the Kaplan-Meier survival analysis and ROC curve indicated that increased SMS level is associated with poor survival rate in HCC and may be a potential
biomarker to discriminate HCC tissues. However, SMS overexpression limited the
therapeutic effect of
immune checkpoint blockade (ICB), which seemed to be related to the immunosuppressive effect of the HCC immune microenvironment formed by higher
mRNA transcript levels of immune checkpoints and higher infiltration levels of immunosuppressive cells. In samples with high and low SMS expression, functional enrichment analysis of the differentially expressed genes (DEGs) showed that SMS may be linked to the occurrence and development of HCC by affecting a variety of immune-related pathways, such as Intestinal immune network for
IgA production, Fc gamma R-mediated phagocytosis, Antigen processing and presentation, Th1 and Th2 cell differentiation. Subsequently, analysis of the co-expression network of SMS in the liver
hepatocellular carcinoma (LIHC) cohort revealed that SMS has a broad impact on multiple important immune- and metabolic-related processes in HCC. In summary, SMS is a promising
biomarker to differentiate the prognosis, immune characteristics, and holds promise as a potential target for ICB
therapy to improve HCC.