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

Edoardo Isnaldi, Domenico Ferraioli, Lorenzo Ferrando, Sylvain Brohée, Fabio Ferrando, Piero Fregatti, Davide Bedognetti, Alberto Ballestrero, Gabriele Zoppoli

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalBreast Cancer Research and Treatment
DOIs
Publication statusPublished - 1 Jan 2019

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Breast Neoplasms
Phenotype
Estrogen Receptors
Drug Therapy
Neoplasms
Gene Ontology
DNA
Thymocytes
Lymphocyte Activation
Nuclear Proteins
Antigen-Antibody Complex
Interferons
Antiviral Agents
Immunity
Biomarkers
T-Lymphocytes
Gene Expression
Cell Line

Keywords

  • Basal-like phenotype
  • Biomarker
  • Breast cancer
  • Immune signatures
  • Schlafen-11

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Schlafen-11 expression is associated with immune signatures and basal-like phenotype in breast cancer. / Isnaldi, Edoardo; Ferraioli, Domenico; Ferrando, Lorenzo; Brohée, Sylvain; Ferrando, Fabio; Fregatti, Piero; Bedognetti, Davide; Ballestrero, Alberto; Zoppoli, Gabriele.

In: Breast Cancer Research and Treatment, 01.01.2019.

Research output: Contribution to journalArticle

Isnaldi, Edoardo ; Ferraioli, Domenico ; Ferrando, Lorenzo ; Brohée, Sylvain ; Ferrando, Fabio ; Fregatti, Piero ; Bedognetti, Davide ; Ballestrero, Alberto ; Zoppoli, Gabriele. / Schlafen-11 expression is associated with immune signatures and basal-like phenotype in breast cancer. In: Breast Cancer Research and Treatment. 2019.
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AU - Ferrando, Lorenzo

AU - Brohée, Sylvain

AU - Ferrando, Fabio

AU - Fregatti, Piero

AU - Bedognetti, Davide

AU - Ballestrero, Alberto

AU - Zoppoli, Gabriele

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