Four genes relevant to pathological grade and prognosis in ovarian cancer

Cancer Biomark. 2020;29(2):169-178. doi: 10.3233/CBM-191162.

Abstract

Background: Ovarian cancer is the common tumor in female, the prognostic of which is influenced by a series of factors. In this study, 4 genes relevant to pathological grade in ovarian cancer were screened out by the construction of weighted gene co-expression network analysis.

Methods: GSE9891 with 298 ovarian cancer cases had been used to construct co-expression networks. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses was used to analyze the possible mechanism of genes involved in the malignant process of ovarian cancer. Hub genes were validated in other independent datasets, such as GSE63885, GSE26193 and GSE30161. Survival analysis based on the hub genes was performed by website of Kaplan Meier-plotter.

Results: The result based on weighted gene co-expression network analysis indicated that turquoise module has the highest association with pathological grade. Gene Ontology enrichment analysis revealed that the genes in turquoise module main enrichment in inflammatory response and immune response. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the genes in turquoise module main enrichment in cytokine-cytokine receptor interaction and chemokine signaling pathway. In turquoise module, a total of 4 hub genes (MS4A4A, CD163, CPR65, MS4A6A) were identified. Then, 4 hub genes were effectively verified in the test datasets (GSE63885, GSE26193 and GSE30161) and tissue samples from Shengjing Hospital of China Medical University. Survival analysis indicated that the 4 hub genes were associated with poor progression-free survival of ovarian cancer.

Conclusions: In conclusion, 4 hub genes (MS4A4A, CD163, CPR65, MS4A6A) were verified associated with pathological grade of ovarian cancer. Moreover, MS4A4A, CD163, MS4A6A may serve as a surface marker for M2 macrophages. Targeting the 4 hub genes may can improve the prognosis of ovarian cancer.

Keywords: M2 macrophages; Ovarian cancer; WGCNA; pathological grade; prognosis.

MeSH terms

  • Antigens, CD / genetics
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Ovarian Epithelial / diagnosis*
  • Carcinoma, Ovarian Epithelial / genetics
  • Carcinoma, Ovarian Epithelial / immunology
  • Carcinoma, Ovarian Epithelial / mortality
  • Cytokines / metabolism
  • Datasets as Topic
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / immunology
  • Gene Regulatory Networks*
  • Humans
  • Kaplan-Meier Estimate
  • Macrophages
  • Membrane Proteins / genetics
  • Neoplasm Grading
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / mortality
  • Prognosis
  • Receptors, Cell Surface / genetics
  • Receptors, G-Protein-Coupled / genetics
  • Signal Transduction / genetics
  • Signal Transduction / immunology

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers, Tumor
  • CD163 antigen
  • Cytokines
  • GPR65 protein, human
  • MS4A4A protein, human
  • MS4A6A protein, human
  • Membrane Proteins
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled