Computational modeling of malignant ascites reveals CCL5-SDC4 interaction in the immune microenvironment of ovarian cancer

Mol Carcinog. 2021 May;60(5):297-312. doi: 10.1002/mc.23289. Epub 2021 Mar 15.

Abstract

Fluid accumulation in the abdominal cavity is commonly found in advanced-stage ovarian cancer patients, which creates a specialized tumor microenvironment for cancer progression. Using single-cell RNA sequencing (scRNA-seq) of ascites cells from five patients with ovarian cancer, we identified seven cell types, including heterogeneous macrophages and ovarian cancer cells. We resolved a distinct polarization state of macrophages by MacSpectrum analysis and observed subtype-specific enrichment of pathways associated with their functions. The communication between immune and cancer cells was predicted through a putative ligand-receptor pair analysis using NicheNet. We found that CCL5, a chemotactic ligand, is enriched in immune cells (T cells and NK cells) and mediates ovarian cancer cell survival in the ascites, possibly through SDC4. Moreover, SDC4 expression correlated with poor overall survival in ovarian cancer patients. Our study highlights the potential role of T cells and NK cells in long-term survival patients with ovarian cancer, indicating SDC4 as a potential prognostic marker in ovarian cancer patients.

Keywords: ascites; intercellular communication; ovarian cancer; single-cell RNA-seq; tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ascites / metabolism
  • Ascites / pathology*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Polarity
  • Chemokine CCL5 / genetics*
  • Chemokine CCL5 / metabolism*
  • Disease Progression
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Killer Cells, Natural / metabolism
  • Macrophages / metabolism
  • Middle Aged
  • Models, Theoretical
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / mortality*
  • Prognosis
  • Sequence Analysis, RNA
  • Single-Cell Analysis / methods
  • Survival Analysis
  • Syndecan-4 / genetics*
  • Syndecan-4 / metabolism*
  • T-Lymphocytes / metabolism
  • Tumor Microenvironment

Substances

  • Biomarkers, Tumor
  • CCL5 protein, human
  • Chemokine CCL5
  • SDC4 protein, human
  • Syndecan-4