Expression of ACAP1 Is Associated with Tumor Immune Infiltration and Clinical Outcome of Ovarian Cancer

DNA Cell Biol. 2020 Sep;39(9):1545-1557. doi: 10.1089/dna.2020.5596. Epub 2020 May 22.

Abstract

ADP-ribosylation factor (Arf) GTPase-activating protein (GAP) with coiled-coil, ankyrin repeat and PH domains 1 (ACAP1) is an Arf6 GAP that regulates membrane trafficking and is critical for the migratory potential of cells. However, the roles of ACAP1 have not been fully explored and its association with clinicopathological features in ovarian cancer is still unknown. In this study, we systematically analyzed multiple databases, including TISIDB, Tumor Immune Estimation Resource (TIMER2.0), Gene Expression Omnibus (GEO), CORTECON, Kaplan-Meier Plotter and LinkedOmics platforms to reveal the clinical significance and function of ACAP1 in ovarian cancer. We found that the expression of ACAP1 was upregulated in ovarian cancer and high ACAP1 expression predicted poor prognosis. Our data demonstrated that the expression and methylation status of ACAP1 were strongly correlated with immune infiltration levels, immunomodulators, and chemokines. Gene set enrichment analysis (GSEA) analysis also showed that the mechanism of ACAP1 in regulating ovarian cancer was related to a variety of immune-related pathways. In addition, we also revealed that the expression of ACAP1 was altered during cell differentiation and associated with cancer cell stemness markers. Our study highlights the clinical significance of ACAP1 in ovarian cancer and provides insight into the novel function of ACAP1 in regulation of tumor immune microenvironment and cancer cell stemness.

Keywords: ACAP1; cell stemness; immune infiltration; ovarian cancer.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Cell Differentiation
  • Chemokines / genetics
  • Chemokines / metabolism
  • DNA Methylation
  • Female
  • GTPase-Activating Proteins / genetics*
  • GTPase-Activating Proteins / metabolism
  • Humans
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Neoplastic Stem Cells / metabolism
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Survival Analysis
  • Tumor Microenvironment
  • Up-Regulation

Substances

  • ACAP1 protein, human
  • Biomarkers, Tumor
  • Chemokines
  • GTPase-Activating Proteins