Exploring Bioinformatics Tools to Analyze the Role of CDC6 in the Progression of Polycystic Ovary Syndrome to Endometrial Cancer by Promoting Immune Infiltration

Int J Mol Sci. 2024 Dec 3;25(23):12974. doi: 10.3390/ijms252312974.

Abstract

Cell division cycle 6 (CDC6) is essential for the initiation of DNA replication in eukaryotic cells and contributes to the development of various human tumors. Polycystic ovarian syndrome (PCOS) is a reproductive endocrine disease in women of childbearing age, with a significant risk of endometrial cancer (EC). However, the role of CDC6 in the progression of PCOS to EC is unclear. Therefore, we examined CDC6 expression in patients with PCOS and EC. We evaluated the relationship between CDC6 expression and its prognostic value, potential biological functions, and immune infiltrates in patients with EC. In vitro analyses were performed to investigate the effects of CDC6 knockdown on EC proliferation, migration, invasion, and apoptosis. CDC6 expression was significantly upregulated in patients with PCOS and EC. Moreover, this protein caused EC by promoting the aberrant infiltration of macrophages into the immune microenvironment in patients with PCOS. A functional enrichment analysis revealed that CDC6 exerted its pro-cancer and pro-immune cell infiltration functions via the PI3K-AKT pathway. Moreover, it promoted EC proliferation, migration, and invasion but inhibited apoptosis. This protein significantly reduced EC survival when mutated. These findings demonstrate that CDC6 regulates the progression of PCOS to EC and promotes immune infiltration.

Keywords: CDC6; endometrial cancer; immune infiltration; polycystic ovarian syndrome.

MeSH terms

  • Apoptosis / genetics
  • Cell Cycle Proteins* / genetics
  • Cell Cycle Proteins* / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation*
  • Computational Biology* / methods
  • Disease Progression*
  • Endometrial Neoplasms* / genetics
  • Endometrial Neoplasms* / immunology
  • Endometrial Neoplasms* / metabolism
  • Endometrial Neoplasms* / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Polycystic Ovary Syndrome* / genetics
  • Polycystic Ovary Syndrome* / immunology
  • Polycystic Ovary Syndrome* / metabolism
  • Polycystic Ovary Syndrome* / pathology
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

  • Cell Cycle Proteins
  • CDC6 protein, human
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-akt