AI Article Synopsis
- Breast cancer (BC) is a complex disease with varying responses to chemotherapy, and Schlafen-11 (SLFN11) is identified as a significant protein linked to treatment sensitivity and immune processes.
- Researchers analyzed data from 5,061 BC patients to explore the relationship between SLFN11 and various immune and pathological factors.
- The study found that high levels of SLFN11 correlate with specific immune responses, a basal-like cancer phenotype, and positive treatment outcomes in estrogen receptor-negative patients, highlighting its potential as a predictive biomarker in BC.
Article 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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| http://dx.doi.org/10.1007/s10549-019-05313-w | DOI Listing |
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