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Clinico-pathological and transcriptomic determinants of SLFN11 expression in invasive breast carcinoma
  1. Gabriele Zoppoli1,
  2. Sylvain Brohee2,
  3. Christine Desmedt2,
  4. Christos Sotiriou2 and
  5. Alberto Ballestrero1
  1. Aff1 grid.5606.50000000121513065Department of Internal Medicine (DiMI)University of Genova Genova Italy
  2. Aff2 grid.418119.4000000010684291XBreast Cancer Translational Research Laboratory J.C. HeusonInstitut Jules Bordet Bruxelles Belgium

https://doi.org/10.1186/2051-1426-3-S1-O3

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    Meeting abstracts

    SLFN11 is a putative DNA/RNA helicase we discovered as causally associated with sensitivity to DNA damaging agents, such as platinum salts, topoisomerase I and II inhibitors, and other alkylators in the NCI-60 panel of cancer cell lines [1]. Later, SLFN11 was identified as an early interferon response gene, in association with HIV infection [2]. Here we assessed SLFN11 determinants in a gene expression meta-set of 5,061 breast cancer patients annotated with clinical data and multigene signatures obtained with the package genefu [3]. By correlation analysis, we found 537 transcripts above the 95th percentile of Pearson’s coefficients with SLFN11, identifying “immune response”, “lymphocyte activation”, and “T cell activation” as top Gene Ontology enriched processes [4]. Through multiple correspondence analysis, we discovered a subgroup of patients characterized by high SLFN11 levels, ER negativity, basal phenotype, elevated CD3D, STAT1 signature [5], and young age. Fitting a penalized maximum likelihood lasso regression model [6], we found a strong multivariable association of SLN11 with the stroma 1 and stroma 2 signatures [7, 8], associated with basal cancer and response to chemotherapy in ER- tumors. Finally, using Cox proportional hazard regression, ER-, high proliferation, high SLFN11 patients undergoing chemotherapy treatment showed a significantly longer disease-free interval than other patient categories included in our model.

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