Date Published: May 4, 2017
Publisher: Public Library of Science
Author(s): Sandra Martínez-Canales, Francisco Cifuentes, Miguel López De Rodas Gregorio, Leticia Serrano-Oviedo, Eva María Galán-Moya, Eitan Amir, Atanasio Pandiella, Balázs Győrffy, Alberto Ocaña, Antonio Perez-Martinez.
Most patients with early stage triple negative breast cancer (TNBC) receive adjuvant chemotherapy. Activation of the immune system is associated with tumor response and may help identify TNBC with favorable outcome.
Gene expression data were obtained from the GEO Dataset GDS2250/GSE3744. Affymetrix CEL files were downloaded and analyzed with Affymetrix Transcriptome Analysis Console 3.0. Functional genomics was implemented with David Bioinformatics Resources 6.8. Data contained at Oncomine were used to identify genes upregulated in basal-like cancer compared to normal breast tissue. Data contained at cBioportal were used to assess for molecular alterations. The KMPlotter online tool, METABRIC and GSE25066 datasets were used to associate gene signatures with clinical outcome.
1564 upregulated genes were identified as differentially expressed between normal and basal-like tumors. Of these, 16 genes associated with immune function were linked with clinical outcome. HLA-C, HLA-F, HLA-G and TIGIT were associated with both improved relapse-free survival (RFS) and overall survival (OS). The combination of HLA-F/TIGIT and HLA-C/HLA-F/TIGIT showed the most favorable outcome (HR for RFS 0.44, p<0.001; HR for OS 0.22, p<0.001; and HR for RFS 0.46, p<0.001; HR for OS 0.15, p<0.001; respectively). The association of HLA-C/HLA-F with outcome was confirmed using the METABRIC and GSE25066 datasets. No copy number alterations of these genes were identified. We describe a gene signature associated with immune function and favorable outcome in basal-like breast cancer. Incorporation of this signature in prospective studies may help to stratify risk of early stage TNBC.
Metastatic triple negative breast cancer (TNBC) is an incurable disease . However, in early stage disease, surgical resection and adjuvant treatment with chemotherapy can contribute to cure in a substantial proportion of patients .
In our study we intended to explore cell surface transmembrane proteins linked with immunological function and outcome. Cell membrane proteins can easily be used as biomarkers and potentially as therapeutic targets. We found that genes that code for membrane receptors involved in the identification of antigens and regulation of immune response were associated with good prognosis. HLA-C, HLA-F, HLA-G and TIGIT are frequently overexpressed in TNBC compared with normal breast and associated with improved RFS and OS in different datasets.