Schlafen-11 expression is associated with immune signatures and basal-like phenotype in breast cancer
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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.
We assessed SLFN11 determinants in a gene expression meta-set of 5061 breast cancer patients annotated with clinical data and multigene signatures.
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.
Our findings are suggestive of a relevant role for SLFN11 in BC and its immune and molecular variability.
KeywordsSchlafen-11 Immune signatures Basal-like phenotype Breast cancer Biomarker
DNA damaging agents
Immunological constant of rejection
Multiple correspondence analysis
Triple-negative breast cancer
GZ would like to thank Dr. P. Blandini, MD, for his invaluable scientific insights during all the phases of this project.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Compliance with ethical standards
Availability of data and material
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.
Conflict of interest
The authors declare no conflict of interest.
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