Immune profiling reveals prognostic genes in high-grade serous ovarian cancer

Aging (Albany NY). 2020 Jun 16;12(12):11398-11415. doi: 10.18632/aging.103199. Epub 2020 Jun 16.

Abstract

High-grade serous ovarian cancer (HGSOC) is a heterogeneous disease with diverse clinical outcomes, highlighting a need for prognostic biomarker identification. Here, we combined tumor microenvironment (TME) scores with HGSOC characteristics to identify immune-related prognostic genes through analysis of gene expression profiles and clinical patient data from The Cancer Genome Atlas and the International Cancer Genome Consortium public cohorts. We found that high TME scores (TMEscores) based on the fractions of immune cell types correlated with better overall survival. Furthermore, differential expression analysis revealed 329 differentially expressed genes between patients with high vs. low TMEscores. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that these genes participated mainly in immune-related functions and, among them, 48 TME-related genes predicted overall survival in HGSOC. Seven of those genes were associated with prognosis in an independent HGSOC database. Finally, the two genes with the lowest p-values in the prognostic analysis (GBP1, ETV7) were verified through in vitro experiments. These findings reveal specific TME-related genes that could serve as effective prognostic biomarkers for HGSOC.

Keywords: ICGC; TCGA; high-grade serous ovarian cancer; overall survival; tumor microenvironment score.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Cell Line, Tumor
  • Cystadenocarcinoma, Serous / genetics
  • Cystadenocarcinoma, Serous / immunology
  • Cystadenocarcinoma, Serous / mortality*
  • Cystadenocarcinoma, Serous / pathology
  • Feasibility Studies
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / immunology*
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Grading
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / mortality*
  • Ovarian Neoplasms / pathology
  • Ovary / immunology
  • Ovary / pathology
  • Prognosis
  • Risk Assessment / methods
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology*

Substances

  • Biomarkers, Tumor