Prognostic Significance of Interferon-γ and Its Signaling Pathway in Early Breast Cancer Depends on the Molecular Subtypes

Int J Mol Sci. 2020 Sep 29;21(19):7178. doi: 10.3390/ijms21197178.

Abstract

Interferons are crucial for adaptive immunity and play an important role in the immune landscape of breast cancer. Using microarray-based gene expression analysis, we examined the subtype-specific prognostic significance of interferon-γ (IFN-γ) as a single gene as well as an IFN-γ signature covering the signaling pathway in 461 breast cancer patients. Prognostic significance of IFN-γ, as well as the IFN-γ signature for metastasis-free survival (MFS), were examined using Kaplan-Meier as well as univariate and multivariate Cox regression analyses in the whole cohort and in different molecular subtypes. The independent prognostic significance of IFN-γ as a single gene was limited to basal-like breast cancer (hazard ratio (HR) 2.779, 95% confidence interval (95% CI) 1.117-6.919, p = 0.028). In contrast, the IFN-γ-associated gene signature was an independent prognostic factor in the whole cohort (HR 2.287, 95% CI 1.410-3.633, p < 0.001) as well as in the basal-like (HR 3.458, 95% CI 1.154-10.359, p = 0.027) and luminal B (HR 2.690, 95% CI 1.416-5.112, p = 0.003) molecular subtypes. These results underline the subtype-dependent prognostic influence of the immune system in early breast cancer.

Keywords: breast cancer; interferon; molecular subtypes; prognosis.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Interferon-gamma / genetics*
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Staging
  • Progression-Free Survival
  • Receptor, ErbB-2 / genetics
  • Receptors, Estrogen / genetics
  • Receptors, Progesterone / genetics
  • Signal Transduction / genetics

Substances

  • Biomarkers, Tumor
  • IFNG protein, human
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Interferon-gamma
  • Receptor, ErbB-2