Identification and Validation of Immune-Related Gene for Predicting Prognosis and Therapeutic Response in Ovarian Cancer

Front Immunol. 2021 Nov 22:12:763791. doi: 10.3389/fimmu.2021.763791. eCollection 2021.

Abstract

Ovarian cancer (OC) is a devastating malignancy with a poor prognosis. The complex tumor immune microenvironment results in only a small number of patients benefiting from immunotherapy. To explore the different factors that lead to immune invasion and determine prognosis and response to immune checkpoint inhibitors (ICIs), we established a prognostic risk scoring model (PRSM) with differential expression of immune-related genes (IRGs) to identify key prognostic IRGs. Patients were divided into high-risk and low-risk groups according to their immune and stromal scores. We used a bioinformatics method to identify four key IRGs that had differences in expression between the two groups and affected prognosis. We evaluated the sensitivity of treatment from three aspects, namely chemotherapy, targeted inhibitors (TIs), and immunotherapy, to evaluate the value of prediction models and key prognostic IRGs in the clinical treatment of OC. Univariate and multivariate Cox regression analyses revealed that these four key IRGs were independent prognostic factors of overall survival in OC patients. In the high-risk group comprising four genes, macrophage M0 cells, macrophage M2 cells, and regulatory T cells, observed to be associated with poor overall survival in our study, were higher. The high-risk group had a high immunophenoscore, indicating a better response to ICIs. Taken together, we constructed a PRSM and identified four key prognostic IRGs for predicting survival and response to ICIs. Finally, the expression of these key genes in OC was evaluated using RT-qPCR. Thus, these genes provide a novel predictive biomarker for immunotherapy and immunomodulation.

Keywords: immune checkpoint inhibitors (ICI); immune-related genes (IRGs); ovarian cancer; prognosis; tumor immune microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computational Biology
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / immunology*
  • Prognosis
  • Proportional Hazards Models

Substances

  • Immune Checkpoint Inhibitors