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Volume 3 Supplement 1

Abstracts of the Breast Cancer Immunotherapy Symposium (BRECIS): Sidra Symposia Series

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Clinico-pathological and transcriptomic determinants of SLFN11 expression in invasive breast carcinoma

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.

References

  1. Zoppoli G, Regairaz M, Leo E, Reinhold WC, Varma S, Ballestrero A, Doroshow JH, Pommier Y: Putative DNA/RNA helicase Schlafen-11 (SLFN11) sensitizes cancer cells to DNA-damaging agents. Proc Natl Acad Sci U S A. 2012, 109 (37): 15030-5. 10.1073/pnas.1205943109.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Li M, Kao E, Gao X, Sandig H, Limmer K, Pavon-Eternod M, Jones TE, Landry S, Pan T, Weitzman MD, David M: Codon-usage-based inhibition of HIV protein synthesis by human schlafen 11. Nature. 2012, 491 (7422): 125-8. 10.1038/nature11433.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Haibe-Kains B, Schroeder M, Bontempi G, Sotiriou C, Quackenbush J: genefu: Relevant Functions for Gene Expression Analysis, Especially in Breast Cancer. 2014, R package version 1.16.0

    Google Scholar 

  4. Huang da W, Sherman BT, Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009, 4 (1): 44-57.

    Article  PubMed  Google Scholar 

  5. Desmedt C, Haibe-Kains B, Wirapati P, Buyse M, Larsimont D, Bontempi G, Delorenzi M, Piccart M, Sotiriou C: Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes. Clin Cancer Res. 2008, 14 (16): 5158-65. 10.1158/1078-0432.CCR-07-4756.

    Article  CAS  PubMed  Google Scholar 

  6. Friedman J, Hastie T, Tibshirani R: Regularization Paths for Generalized Linear Models via Coordinate Descent. J Stat Softw. 2010, 33 (1): 1-22.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Farmer P, Bonnefoi H, Anderle P, Cameron D, Wirapati P, Becette V, André S, Piccart M, Campone M, Brain E, Macgrogan G, Petit T, Jassem J, Bibeau F, Blot E, Bogaerts J, Aguet M, Bergh J, Iggo R, Delorenzi M: A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer. Nat Med. 2009, 15 (1): 68-74. 10.1038/nm.1908.

    Article  CAS  PubMed  Google Scholar 

  8. Finak G, Bertos N, Pepin F, Sadekova S, Souleimanova M, Zhao H, Chen H, Omeroglu G, Meterissian S, Omeroglu A, Hallett M, Park M: Stromal gene expression predicts clinical outcome in breast cancer. Nat Med. 2008, 14 (5): 518-27. 10.1038/nm1764.

    Article  CAS  PubMed  Google Scholar 

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Zoppoli, G., Brohee, S., Desmedt, C. et al. Clinico-pathological and transcriptomic determinants of SLFN11 expression in invasive breast carcinoma. j. immunotherapy cancer 3 (Suppl 1), O3 (2015). https://doi.org/10.1186/2051-1426-3-S1-O3

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