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A novel HCC prognosis predictor PDSS1 affects the cell cycle through the STAT3 signaling pathway in HCC

Zuqin Rao1,2, Heng Li3, Wenchao Yao1,2

  • 1Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Frontiers in Oncology
|August 15, 2022
PubMed

Insights

Decaprenyl diphosphate synthase subunit 1 (PDSS1) is upregulated in hepatocellular carcinoma (HCC), correlating with poor prognosis and increased immune cell infiltration. PDSS1 knockdown inhibits HCC cell proliferation, migration, and invasion, suggesting it as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Decaprenyl diphosphate synthase subunit 1 (PDSS1) is implicated in human diseases, but its role in hepatocellular carcinoma (HCC) remains uncharacterized.
  • Understanding PDSS1's function in HCC is crucial for identifying novel biomarkers and therapeutic strategies.

Purpose of the Study:

  • To investigate the expression pattern, biological function, and prognostic significance of PDSS1 in HCC.
  • To explore the relationship between PDSS1 and immune infiltration in the HCC microenvironment.

Main Methods:

  • Analysis of PDSS1 expression using TCGA and GEO databases.
  • Correlation analysis of PDSS1 with clinicopathological characteristics and patient survival.
  • Gene Set Enrichment Analysis (GSEA) and assessment of immune cell infiltration using GSVA.
  • In vitro functional assays (EdU, colony formation, Transwell, wound healing, flow cytometry) to evaluate PDSS1's impact on HCC cell phenotype.
  • Investigation of PDSS1's role in oncogenic pathways, including STAT3 signaling.

Main Results:

  • PDSS1 was significantly upregulated in HCC tissues compared to adjacent non-tumorous tissues.
  • High PDSS1 expression correlated with unfavorable overall survival, disease-specific survival, and progression-free interval in HCC patients.
  • PDSS1 knockdown suppressed HCC cell proliferation, cell cycle progression, migration, and invasion, indicating its oncogenic role.
  • PDSS1 expression was associated with various immune cells, including Th2, TFH, T helper cells, NK cells, cytotoxic cells, dendritic cells, CD8 T cells, and neutrophils.
  • PDSS1 promotes tumorigenesis in HCC, potentially through the STAT3 signaling pathway.

Conclusions:

  • Elevated PDSS1 levels in HCC are linked to poor patient prognosis and altered immune cell infiltration.
  • PDSS1 functions as an oncogene in HCC, impacting cell proliferation, cycle, and invasion.
  • PDSS1 represents a promising novel biomarker and potential therapeutic target for hepatocellular carcinoma.

Keywords:
PDSS1STAT3cell cycleimmune infiltrationprognosis

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