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Volume 3 Supplement 1

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

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Systems biology analysis of gene expression data and gene network reverse-engineering approaches reveal NFAT5 as a candidate biomarker in Inflammatory Breast Cancer

Journal for ImmunoTherapy of Cancer volume 3, Article number: P6 (2015) Cite this article

Inflammatory Breast Cancer (IBC) is the most aggressive and highly metastatic form of breast cancer [1–3]. In a recent study [4], we analysed breast cancer with peritumoral neoplastic lymphovascular invasion (ePVI) in comparison with inflammatory breast cancer, showing that ePVI breast cancer have more clinicopathologic affinity than differences with the most aggressive cancer in the breast. Here, we aim to identify potential master regulators (MRs) that drive the expression pattern in IBC.

Transcriptomic (i.e., mRNA) data from 197 breast tumours were used for this analysis (GEO GSE23720) [5]. All tumours were classified as “IBC” (n=63) or “nIBC” (n=134). To identify novel MRs that drive the IBC phenotype, all expression data were analysed using a network-based strategy (ARACNe [6]) and Master Regulator Analysis (MRA)[7]. We chose to perform in-vivo IHC analysis, in two independent cohorts of IBCs (n = 39), nIBCs (n = 82) and normal breast tissues (n = 15), for the top significant Master Regulators: MGA, CTNNB1 and NFAT5. Biological validation confirmed that NFAT5 expression was higher in IBC than in nIBC (70% vs. 20%) and that the majority of NFAT5-positive IBC samples displayed NFAT5 nuclear expression in comparison with nIBC samples (89% vs. 12%).

We provide evidence that NFAT5 transcription factor could constitute a novel IBC biomarker that could help to identify the most aggressive forms of BC into routine clinical practice.

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Author notes

    Authors and Affiliations

    1. Department of Pathology, Mater Salutis Hospital, Legnago, Italy

      Andrea Remo

    2. Qatar Computing Research Institute (QCRI), Qatar Foundation, Doha, Qatar

      Ines Simeone, Halima Bensmail & Michele Ceccarelli

    3. Department of Science and Technology, University of Sannio, Benevento, Italy

      Massimo Pancione, Luigi Cerulo & Vittorio Colantuoni

    4. Department of Pathology and Diagnosis, University of Verona, Verona, Italy

      Pietro Parcesepe, Franco Bonetti & Erminia Manfrin

    5. Department of Molecular Oncology, Institut Paoli-Calmettes, U1068 Inserm, Marseille, France

      Pascal Finetti, Daniel Birnbaum & Francois Bertucci

    Authors
    1. Andrea Remo
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    2. Ines Simeone
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    3. Massimo Pancione
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    4. Pietro Parcesepe
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    5. Pascal Finetti
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    6. Halima Bensmail
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    7. Luigi Cerulo
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    8. Vittorio Colantuoni
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    9. Daniel Birnbaum
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    10. Franco Bonetti
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    11. Francois Bertucci
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    12. Erminia Manfrin
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    13. Michele Ceccarelli
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    Additional information

    Andrea Remo, Ines Simeone, Massimo Pancione and Michele Ceccarelli contributed equally to this work.

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    Cite this article

    Remo, A., Simeone, I., Pancione, M. et al. Systems biology analysis of gene expression data and gene network reverse-engineering approaches reveal NFAT5 as a candidate biomarker in Inflammatory Breast Cancer. j. immunotherapy cancer 3 (Suppl 1), P6 (2015). https://doi.org/10.1186/2051-1426-3-S1-P6

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    • DOI: https://doi.org/10.1186/2051-1426-3-S1-P6

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