PTDSS1 serves as a prognostic biomarker of macrophage infiltration in pan-cancer and promotes hepatocellular carcinoma malignant phenotypes.

BACKGROUND: Phosphatidylserine synthase 1 (PTDSS1) inhibitor has been developed and shows promising anti-tumor effect, but existing studies about PTDSS1 remain limited in cancer. METHODS: This study preliminarily analyzed the differential expression, prognostic significance, copy number variation, methylation level, co-expression network and immune correlation of PTDSS1 in pan-cancer. Furthermore, we collected tumor samples and corresponding clinical information of 74 hepatocellular carcinoma (HCC) patients from the First Hospital of Guangxi Medical University (Guangxi cohort) to validate PTDSS1 expression and prognostic value. In vitro experiments were performed to investigate the effect of PTDSS1 knockdown on the malignant phenotypes of HCC cell lines. RESULTS: This study identified that PTDSS1 was significantly upregulated across most cancer types and associated with poor prognosis of seven cancer types. Copy number amplification and hypermethylation of PTDSS1 may drive its upregulation. Furthermore, PTDSS1 exhibited a positive correlation with macrophage in various cancers, co-expression network and functional enrichment analysis revealed that PTDSS1 may involve in cell division, cell cycle, DNA repair, cell proliferation, cell migration, cell growth, immune response and WNT signaling pathway. Regarding HCC, the differential expression and prognostic significance of PTDSS1 were verified by Guangxi cohort, single cell sequencing analysis revealed PTDSS1 located in tumor cell and macrophages. In vitro experiments demonstrated that PTDSS1 knockdown suppressed the proliferation, migration, invasion of HCC cells and promoted macrophage repolarization towards the M1 phenotype. CONCLUSIONS: PTDSS1 serves as a diagnostic and prognostic biomarker associated with macrophage infiltration, and may be a promising therapeutic target.