CD47 and SIRPα (signal-regulatory protein) are tumor biomarkers of innate immunity, expressed on cancer cells and tumor associated macrophages (TAMs); their interaction provides a “don’t eat me” signal that impairs phagocytosis. The relationship between CD47/SIRPα expression and BC aggressiveness has been investigated, however, its prognostic role is not clarified. With these premises, we have assessed the distribution and the possible prognostic value of CD47/SIRPα expression in early BC.
To verify our hypothesis, we first used in silico data from GOBO and GEPIA, two publicly available datasets: GOBO is a public repository containing microarray data (Affymetrix U133A) from 1881 early BC patients, with a median follow up of 120 months. GEPIA is a web server for analysing RNA expression data of tumours and normal samples from the TCGA and the GTEx projects, by a standard processing pipeline. Immunohistochemical (IHC) analyses were retrospectively performed on formalin-fixed paraffin embedded tissue (FFPE) samples in a cohort of 105 BC patients referred to our institution. The association between CD47 and SIRPα expression levels and outcome was evaluated using the χ2 test. Disease free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier life table method.
In silico data showed that CD47 and SIRPα are preferentially expressed in triple negative (TN) BC, as compared to other BC subtypes (p< 0.0001). CD47 upregulation is associated to a worse OS only in Luminal A BC (GOBO p<0.001, n= 189 patients). By IHC analysis in our retrospective series, CD47 was overexpressed in 80% of TNBC and in 56% of Luminal BC samples. Of note, SIRPα was expressed in 20% of TAMs and in 50% of TN BC samples.
Biomarkers of innate immunity are represented but differently expressed in the different BC subtypes; IHC analyses are ongoing to consolidate this result and to assess their prognostic role in our patient cohort. Final analyses will be presented.
The authors.
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All authors have declared no conflicts of interest.