The Potential Role of Complement System in the Progression of Ovarian Clear Cell Carcinoma Inferred from the Gene Ontology-Based Immunofunctionome Analysis

Int J Mol Sci. 2020 Apr 17;21(8):2824. doi: 10.3390/ijms21082824.


Ovarian clear cell carcinoma (OCCC) is the second most common epithelial ovarian carcinoma (EOC). It is refractory to chemotherapy with a worse prognosis after the preliminary optimal debulking operation, such that the treatment of OCCC remains a challenge. OCCC is believed to evolve from endometriosis, a chronic immune/inflammation-related disease, so that immunotherapy may be a potential alternative treatment. Here, gene set-based analysis was used to investigate the immunofunctionomes of OCCC in early and advanced stages. Quantified biological functions defined by 5917 Gene Ontology (GO) terms downloaded from the Gene Expression Omnibus (GEO) database were used. DNA microarray gene expression profiles were used to convert 85 OCCCs and 136 normal controls into to the functionome. Relevant offspring were as extracted and the immunofunctionomes were rebuilt at different stages by machine learning. Several dysregulated pathogenic functions were found to coexist in the immunopathogenesis of early and advanced OCCC, wherein the complement-activation-alternative-pathway may be the headmost dysfunctional immunological pathway in duality for carcinogenesis at all OCCC stages. Several immunological genes involved in the complement system had dual influences on patients' survival, and immunohistochemistrical analysis implied the higher expression of C3a receptor (C3aR) and C5a receptor (C5aR) levels in OCCC than in controls.

Keywords: complement system; gene ontology (GO); immunological function; machine learning; ovarian clear cell carcinoma (OCCC).

MeSH terms

  • Adenocarcinoma, Clear Cell / genetics*
  • Adenocarcinoma, Clear Cell / immunology
  • Adenocarcinoma, Clear Cell / mortality
  • Case-Control Studies
  • Complement C3a / genetics*
  • Complement C3a / metabolism
  • Disease Progression
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Gene Ontology
  • Humans
  • Machine Learning
  • Oligonucleotide Array Sequence Analysis
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / mortality
  • Receptors, Complement / genetics*
  • Receptors, Complement / metabolism
  • Survival Analysis


  • Receptors, Complement
  • Complement C3a