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.
Highlights
The immune system plays a decisive, and ambivalent role in tumorigenesis as well as in tumor elimination of solid tumors [1]
In a previous gene expression study, we identified a B-cell metagene that was correlated with improved metastasis-free survival (MFS) in highly proliferating node-negative breast cancer patients regardless of estrogen receptor (ER) or human epidermal growth factor receptor 2 (HER2) status [9]
We showed in this retrospective gene expression study that IFN-γ as a single gene had significant prognostic influence only in basal-like breast cancer
Summary
The immune system plays a decisive, and ambivalent role in tumorigenesis as well as in tumor elimination of solid tumors [1]. To obtain a complete picture of the prognostic role of IFN‐γ in the immune landscape of breast cancer, we defined an IFN‐γ signature that includes the abovementioned genes. This prompted us to evaluTaoteobthtaeinpraocgonmosptliectesipgincitfuicraenocfethoef pIFrNog‐nγoasntidc raonleIoFfNIF‐γN‐a-γssioncitahteedimgmenuenesilgannadtsucraepienoaf bwreealls‐t cchaanrcaecrt,ewrizeedecfionheodrt aonf 4I6F1Np-γatiseingtnsawtuirthe etharaltyibnrceluasdtecsanthcera. High expression of the IFN‐-γ signature had an independent infflluence on MFS in a multivariate analysis adjusted for age, tumor size, axillary nodal status, and histological grade of difffferentiation both in basal-‐like breast cancer (HR 3.458,, 95%% CI 1.154––1100..335599,, pp == 0.027) as well as luminal B tumors (HR 2.690, 95% CI 1.416–5.112, p = 0.003; Table 4).
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