Abstract
OBJECTIVES: The expression of sphingomyelin phosphodiesterase 4 (SMPD4), a neutral sphingomyelin enzyme, is intricately associated with tumorigenesis and progression. However, its role in hepatocellular carcinoma (HCC) remains unclear. This study mainly reports the expression, prognostic value and tumor biological function of SMPD4 in HCC. METHODS: The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and International Cancer Genome Consortium (ICGC) databases were utilized to investigate the expression patterns of SMPD4. Survival Analyses using the Kaplan-Meier method were conducted to assess the predictive value of SMPD4 in HCC. Immunohistochemistry method and real-time quantitative PCR were used to analyze the expression of SMPD4 in our clinical cohort. Immune infiltration analysis was performed to explore the correlation between SMPD4 expression and immune cell infiltration in HCC. Functional enrichment analysis was conducted to depict SMPD4-associated functions and pathways. Using human HCC cell lines, we studied the influence of SMPD4 in cell proliferation, invasion and migration. RESULTS: We found SMPD4 was overexpressed in HCC. The Kaplan-Meier curves demonstrated that higher expression of SMPD4 was associated with worse survival in patients with HCC. Immune infiltration analysis showed that SMPD4 expression exhibited positive correlations with CD4 + T cells, Type 2 T helper cells, and negatively related to neutrophil, eosinophil, nature killer cells, macrophage, activated CD8 T cells. Functional enrichment analysis revealed that SMPD4 expression is associated with cell cycle pathways. Additionally, cell functional studies in HCC cell lines indicated that the knockdown of SMPD4 significantly inhibited cell growth, invasion and migration. CONCLUSIONS: These results reveal that high SMPD4 expression is associated with poor prognosis and promotes HCC cell proliferation, invasion and migration. SMPD4 is a promising prognostic biomarker with functional significance for HCC.