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

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...

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Bibliographic Details
Published in:	International journal of molecular sciences 2020-09, Vol.21 (19), p.7178
Main Authors:	Heimes, Anne-Sophie, Härtner, Franziska, Almstedt, Katrin, Krajnak, Slavomir, Lebrecht, Antje, Battista, Marco J, Edlund, Karolina, Brenner, Walburgis, Hasenburg, Annette, Sahin, Ugur, Gehrmann, Mathias, Hengstler, Jan G, Schmidt, Marcus
Format:	Article
Language:	eng
Subjects:	Adaptive immunity Aged Apoptosis Biomarkers, Tumor - genetics Breast cancer Breast Neoplasms - epidemiology Breast Neoplasms - genetics Breast Neoplasms - pathology Chemokines Confidence intervals Cytokines Disease-Free Survival DNA microarrays Estrogens Female Gene expression Gene Expression Regulation, Neoplastic - genetics Humans Immune system Interferon Interferon-gamma - genetics Kaplan-Meier Estimate Kinases Ligands Medical prognosis Metastases Middle Aged molecular subtypes Multivariate analysis Neoplasm Staging prognosis Progression-Free Survival Proteins Receptor, ErbB-2 - genetics Receptors, Estrogen - genetics Receptors, Progesterone - genetics Regression analysis Signal transduction Signal Transduction - genetics Signaling Statistical analysis Tumors γ-Interferon
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Summary:	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, = 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, < 0.001) as well as in the basal-like (HR 3.458, 95% CI 1.154-10.359, = 0.027) and luminal B (HR 2.690, 95% CI 1.416-5.112, = 0.003) molecular subtypes. These results underline the subtype-dependent prognostic influence of the immune system in early breast cancer.
ISSN:	1422-0067 1661-6596 1422-0067