Transcriptomic immunologic signature associated with favorable clinical outcome in basal-like breast tumors

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

doi:10.1371/journal.pone.0175128

Transcriptomic immunologic signature associated with favorable clinical outcome in basal-like breast tumors

PLoS One. 2017 May 4;12(5):e0175128. doi: 10.1371/journal.pone.0175128. eCollection 2017.

Affiliations

¹ Translational Research Unit, Albacete University Hospital and CIBERONC, Albacete, Spain.
² Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha, Albacete, Spain.
³ Princess Margaret Cancer Center, University of Toronto, Toronto, Canada.
⁴ Cancer Research Center and CIBERONC, CSIC-University of Salamanca, Salamanca, Spain.
⁵ MTA TTK Lendület Cancer Biomarker Research Group, Budapest, Hungary.
⁶ Semmelweis University 2nd Dept. of Pediatrics, Budapest, Hungary.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

MeSH terms

Breast Neoplasms / genetics
Breast Neoplasms / immunology*
Female
Humans
Transcriptome*
Treatment Outcome*
Up-Regulation

Grants and funding

This study was supported in part by the Instituto de Salud Carlos III (PI16/0121), ACEPAIN; Diputación de Albacete and CRIS Cancer Foundation (to AO). BAE (Beca Ampliación de Estudios) and Spanish Society of Medical Oncology (SEOM) to AO for his stay at Yale University. Ministry of Economy and Competitiveness of Spain (BFU2015-71371-R), the Instituto de Salud Carlos III through the Spanish Cancer Centers Network Program (RD12/0036/0003) and CIBERONC, the scientific foundation of the AECC and the CRIS Foundation (to AP). The work carried out in our laboratories received support from the European Community through the regional development funding program (FEDER). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.