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Schlafen-11 expression is associated with immune signatures and basal-like phenotype in breast cancer

  • Preclinical study
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Breast Cancer Research and Treatment Aims and scope Submit manuscript

A Correction to this article was published on 12 July 2019

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Abstract

Purpose

Breast cancer (BC) is a heterogeneous disorder, with variable response to systemic chemotherapy. Likewise, BC shows highly complex immune activation patterns, only in part reflecting classical histopathological subtyping. Schlafen-11 (SLFN11) is a nuclear protein we independently described as causal factor of sensitivity to DNA damaging agents (DDA) in cancer cell line models. SLFN11 has been reported as a predictive biomarker for DDA and PARP inhibitors in human neoplasms. SLFN11 has been implicated in several immune processes such as thymocyte maturation and antiviral response through the activation of interferon signaling pathway, suggesting its potential relevance as a link between immunity and cancer. In the present work, we investigated the transcriptional landscape of SLFN11, its potential prognostic value, and the clinico-pathological associations with its variability in BC.

Methods

We assessed SLFN11 determinants in a gene expression meta-set of 5061 breast cancer patients annotated with clinical data and multigene signatures.

Results

We found that 537 transcripts are highly correlated with SLFN11, identifying “immune response”, “lymphocyte activation”, and “T cell activation” as top Gene Ontology processes. We established a strong association of SLFN11 with stromal signatures of basal-like phenotype and response to chemotherapy in estrogen receptor negative (ER-) BC. We identified a distinct subgroup of patients, characterized by high SLFN11 levels, ER- status, basal-like phenotype, immune activation, and younger age. Finally, we observed an independent positive predictive role for SLFN11 in BC.

Conclusions

Our findings are suggestive of a relevant role for SLFN11 in BC and its immune and molecular variability.

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Change history

  • 12 July 2019

    In the original publication of the article, the funding information was incorrectly published. The corrected funding statement is given in this correction article.

Abbreviations

BC:

Breast cancer

DDA:

DNA damaging agents

DFS:

Disease-free survival

ER:

Estrogen receptor

HT:

Hormone treatment

ICR:

Immunological constant of rejection

MCA:

Multiple correspondence analysis

SLFN11:

Schlafen-11

TNBC:

Triple-negative breast cancer

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Acknowledgements

GZ would like to thank Dr. P. Blandini, MD, for his invaluable scientific insights during all the phases of this project.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Author notes

  1. Edoardo Isnaldi, Domenico Ferraioli, Lorenzo Ferrando, Alberto Ballestrero and Gabriele Zoppoli contributed equally to the present work.

Authors and Affiliations

  1. Department of Internal Medicine (DiMI), University of Genoa and Ospedale Policlinico San Martino, Viale Benedetto XV, 6, 16132, Genoa, Italy

    Edoardo Isnaldi, Domenico Ferraioli, Lorenzo Ferrando, Fabio Ferrando, Piero Fregatti, Alberto Ballestrero & Gabriele Zoppoli

  2. Comprehensive Cancer Center Leon Berard, Lyon, France

    Domenico Ferraioli

  3. Institut de Pathologie Et de Génétique a.s.b.l, Charleroi, Belgium

    Sylvain Brohée

  4. Ospedale Policlinico San Martino IRCCS per l’Oncologia, Genoa, Italy

    Fabio Ferrando, Piero Fregatti, Alberto Ballestrero & Gabriele Zoppoli

  5. Sidra Medical Center, Doha, Qatar

    Davide Bedognetti

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  1. Edoardo Isnaldi
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  2. Domenico Ferraioli
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Correspondence to Gabriele Zoppoli.

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All raw data used for the generation of the expression set we analyzed are available in GEO under their respective publication IDs. Normalized expression data are available upon request to the Corresponding Author.

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Isnaldi, E., Ferraioli, D., Ferrando, L. et al. Schlafen-11 expression is associated with immune signatures and basal-like phenotype in breast cancer. Breast Cancer Res Treat 177, 335–343 (2019). https://doi.org/10.1007/s10549-019-05313-w

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