Comprehensive Analysis of the Control of Cancer Stem Cell Characteristics in Endometrial Cancer by Network Analysis

Comput Math Methods Med. 2021 Mar 29:2021:6653295. doi: 10.1155/2021/6653295. eCollection 2021.

Abstract

Background: Cancer stem cells play an important role in endometrial cancer (EC). It is closely related to self-renewal and therapeutic resistance of EC.

Methods: In this study, WGCNA (weighted gene coexpression network analysis) was used to analyze the relationship between genes and clinical features. We also performed immune cell infiltration analysis of a key module by using ImmuCellAI (Immune Cell Abundance Identifier). Then, key genes were verified in the GEO database. Finally, causal relationship analysis and protein-protein interaction analysis were performed in DisNor tool and STRING.

Result: The mRNA expression-based stemness index (mRNAsi) is significantly lower in normal tissues and is significantly higher in individuals with stage IV or high-grade cancer and those who are obese or postmenopausal. Nineteen key genes (ORC6, C1orf112, RAD54L, SGO2, BUB1, PLK4, KIF18B, BUB1B, TTK, NCAPG, XRCC2, CENPF, KIF15, RACGAP1, ARHGAP11A, TPX2, KIF14, KIF4A, and NCAPH) that were enriched mainly in terms related to the cell cycle and DNA replication were selected by weighted gene coexpression network analysis (WGCNA). Based on the key modules, the numbers of NKT cells, NK cells, and neutrophils in the normal group were significantly higher than those in the cancer group. PLK1, CDK1, and MAD2L1, which were correlated with upstream genes, may be an regulated upstream of key genes.

Conclusion: PLK1, CDK1, and MAD2L1 which were strongly correlated with upstream genes may be a regulated upstream of key genes.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Cell Cycle / genetics
  • Computational Biology
  • DNA Replication / genetics
  • Databases, Genetic / statistics & numerical data
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Neoplastic Stem Cells / immunology
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Pregnancy
  • Protein Interaction Maps / genetics
  • RNA, Messenger / genetics

Substances

  • Biomarkers, Tumor
  • RNA, Messenger